bluuebunny/crossref_metadata_2025_split huggingface dataset:
KSHV RTA utilizes the host E3 ubiquitin ligase complex RNF20/40 to drive lytic reactivation
Authors: Spires Lauren McKenzie , Wind Eleanor , Papp Bernadett , Toth Zsolt 
Published: October 2023

ABSTRACT
Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus whose lytic replication cycle is induced and driven by the viral transcription factor RTA (replication and transcription activator). Identifying what cellular and viral proteins RTA is interacting with during lytic reactivation can help to better understand how RTA promotes the lytic cycle. Using a proteomic approach, we identified the cellular E3 ubiquitin ligase complex RNF20/40 as a novel interacting partner of RTA. One of the major roles of this protein complex is the monoubiquitylation of histone H2B at lysine 120 on cellular chromatin, which is a hallmark of transcriptionally active genes. While the role of RNF20/40 has been studied on different host genomes, its potential to regulate viral genes remains largely unexplored. Here, we show that the shRNA inhibition of RNF20 expression impairs RTA-induced host and viral lytic gene expression, viral DNA replication, and virus production. In addition, we found that the association of RNF20 with the KSHV episome increases during lytic reactivation, and the binding of RTA to viral promoters is required for the synergistic promoter activation by RTA and RNF20/40. Interestingly, the inhibition of RNF20 expression during lytic reactivation of KSHV did not affect H2BK120ub level but it did reduce RNA polymerase II occupancy on viral promoters. Overall, our data suggest that RTA is hijacking the cellular E3 ligase complex RNF20/40 to increase the level of transcriptionally active RNA polymerase II on viral gene promoters thereby facilitating lytic gene expression to advance the viral lytic cycle.

IMPORTANCE
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-causing human herpesvirus that establishes a persistent infection in humans. The lytic viral cycle plays a crucial part in lifelong infection as it is involved in the viral dissemination. The master regulator of the KSHV lytic replication cycle is the viral replication and transcription activator (RTA) protein, which is necessary and sufficient to push the virus from latency into the lytic phase. Thus, the identification of host factors utilized by RTA for controlling the lytic cycle can help to find novel targets that could be used for the development of antiviral therapies against KSHV. Using a proteomics approach, we have identified a novel interaction between RTA and the cellular E3 ubiquitin ligase complex RNF20/40, which we have shown to be necessary for promoting RTA-induced KSHV lytic cycle.
Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study
Authors: Gurram Venkata Sujith Kumar Reddy , Lodha Abhay , Hicks Matthew , Jain Amish , Lapointe Anie , Makary Hala , Kanungo Jaideep , Lee Kyong-Soon , Ye Xiang , Shah Prakesh S , Soraisham Amuchou S 
Published: October 2023

ObjectiveTo assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).MethodsIn this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18–24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO.ResultsOf the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18–24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12).ConclusionsIn preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18–24 months CA.
Xylitol for the prevention of acute otitis media episodes in children aged 1–5 years: a randomised controlled trial
Authors: Persaud Navindra , Azarpazhooh Amir , Keown-Stoneman Charles , Birken Catherine S , Isaranuwatchai Wanrudee , Maguire Jonathon L , Mamdani Muhammad , Allen Christopher , Mason Dalah , Kowal Christine , Jaleel Mateenah , Bazeghi Farnaz , Thorpe Kevin E , Laupacis Andreas , Parkin Patricia C 
Published: October 2023

ObjectiveTo investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries.DesignBlinded randomised controlled trial with a 6-month study period.SettingEnrolment took place at 11 primary care practices in Ontario, Canada.PatientsChildren aged 1–5 years who did not use xylitol or sorbitol at enrolment.InterventionsChildren were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months.Main outcome measuresPrimary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries.ResultsAmong the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol).ConclusionsRegular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious.Trial registration numberNCT03055091.
Outcomes of low-level light therapy before and after cataract surgery for the prophylaxis of postoperative dry eye: a prospective randomised double-masked controlled clinical trial
Authors: Giannaccare Giuseppe , Rossi Costanza , Borselli Massimiliano , Carnovale Scalzo Giovanna , Scalia Giovanni , Pietropaolo Rocco , Fratto Benedetta , Pellegrini Marco , Yu Angeli Christy , Scorcia Vincenzo 
Published: October 2023

BackgroundDespite increasing evidence shows that optimising ocular surface before cataract surgery is fundamental in patients with pre-existing dry eye disease (DED) to achieve the desired postoperative outcomes, the prophylactic treatment of healthy patients undergoing surgery aiming at preventing iatrogenic DED is worth investigating.MethodsThis was a prospective, interventional, randomised, controlled, double-masked clinical trial. Patients were randomly assigned 1:1 to receive either low-level light therapy (LLLT) or sham treatment (LLLT with a power output <30%). Patients underwent two treatment sessions: 7±2 days before cataract surgery (T0) and 7±2 days after (T1). Outcome measures evaluated 30±4 days after surgery (T2) included Ocular Surface Disease Index (OSDI) questionnaire, non-invasive break-up time (NIBUT), tear meniscus height, meibomian gland loss (MGL) and redness score.ResultsOut of 153 patients randomised to receive LLLT (n=73) or sham treatment (n=80), 131 (70 men, 61 women, mean age 73.53±7.29 years) completed regularly the study. Patients treated with LLLT had significantly lower OSDI scores compared with controls at T1 and T2 (respectively, 7.2±8.8 vs 14.8±13.0 and 9.0±9.0 vs 18.2±17.9; both p<0.001), higher NIBUT values at T2 (12.5±6.6 vs 9.0±7.8; p=0.007) and lower MGL Meiboscore values at T1 (1.59±0.70 vs 1.26±0.69; p=0.008). Unlike controls, patients treated with LLLT had significantly lower OSDI scores and higher NIBUT values at T2 compared with T0 (respectively, 9.0±9.0 vs 21.2±16.1; p<0.001 and 12.5±6.6 vs 9.7±7.2; p=0.007).ConclusionTwo sessions of LLLT performed before and after cataract surgery were effective in ameliorating tear film stability and ocular discomfort symptoms.Trial registration numberNCT05754437.
Ultrasound Directed Reduction of Colles’ type distal radial fractures in ED (UDiReCT): a feasibility randomised controlled trial
Authors: Malik Hamza , Wood Darryl , Stone Oliver , Gough Anthony , Taylor Gordon , Knapp Karen M , Heggs Daniel , Appelboam Andrew 
Published: October 2023

BackgroundThere is a high rate of surgical fixation of displaced Colles’ type distal radial wrist fractures despite fracture manipulation in the ED. Point-of-care ultrasound has been used to guide ED manipulations but its effect on the quality of fracture reduction or subsequent need for surgical fixation is unknown. This study aims to assess the feasibility of conducting a definitive randomised controlled trial to assess the use of ultrasound to guide these fracture manipulations.MethodsWe conducted a pragmatic randomised controlled feasibility trial in two EDs in England over a 6-month period (7 October 2019 to 6 April 2020). Adult patients with wrist fractures undergoing manipulation in the ED were randomised 1:1 to ultrasound-guided distal radial fracture manipulation or manipulation with sham ultrasound. The primary outcome for this study was trial recruitment rate. Other measures were recorded to assess potential future definitive trial outcomes and feasibility.ResultsOf 120 patients meeting inclusion criteria, 48 (40%) were recruited and randomised in the two centres, giving overall recruitment rates of 0.3 and 1.8 participants per week at each site, respectively, and 1 participant per week overall. The most common reason that patients were not included was research staff availability. After 6 weeks, six patients in each group (26% intervention, 24% control) had undergone surgical fixation, with 98% data completeness for this potential definitive trial primary outcome. Randomisation, blinding and data collection processes were effective but there were data limitations in the X-ray assessment of fracture positions.ConclusionA definitive study of a similar design would be feasible within UK ED practice but organisational factors and research staff availability should be considered when estimating the predicted recruitment rate and required sites. 6-week surgical fixation rate was the most reliable outcome measure.Trial registrationClinicalTrials.gov (NCT03868696).
Installation and capacity performance of multi-line dynamically installed anchors
Authors: Liu Jun , Li Yunfei , Guo Xinshuai , Han Congcong 
Published: October 2023

The multi-line anchor achieves the “anchor sharing” goal by allowing multiple floating devices to be moored, such that the total number of anchors in a floating device array can be reduced significantly. This study proposes a dynamically installed anchor with the potential of resisting uplift loading from varied directions. The multi-line anchor is dynamically installed with the aid of a booster. The installation performance of the hybrid anchor (i.e., multi-line anchor + booster) is first examined by field tests. Then, finite-element analyses are performed to investigate the uplift capacity of the anchor under V-H-M-T combined loading conditions. Based on the numerical results, yield envelopes are established for assessing the ultimate bearing capacity of the anchor. Additionally, model tests are conducted to quantitatively study the installation and setup effects on the uplift capacity of the anchor, indicating that the vertical and torque capacities are sensitive to the installation effect. Finally, a design framework is proposed to assess the stability of the multi-line anchor under combined loading conditions.
Matrix element corrections in the Pythia8 parton shower in the context of matched simulations at next-to-leading order
Authors: Frixione Stefano , Amoroso Simone , Mrenna Stephen 
Published: October 2023

AbstractWe discuss the role of matrix element corrections (MEC) to parton showers in the context of MC@NLO-type matchings for processes that feature unstable resonances, where MEC are liable to result in double-counting issues, and are thus generally not employed. By working with Pythia8, we show that disabling all MEC is actually unnecessary in computations based on the narrow-width approximation, and we propose alternative MEC settings which, while still avoiding double counting, allow one to include hard-recoil effects in the simulations of resonance decays. We illustrate our findings by considering $$t\bar{t}$$

t

t

¯

production at the LHC, and by comparing MadGraph5-aMC@NLO predictions with those of POWHEG-BOX and standalone Pythia8.
IoT-Enabled Deep Learning Algorithm for Estimation of State-of-Charge of Lithium-ion Batteries
Authors: Pushpavanam B. , Kalyani S. , Prasanna M. Arul , Sangaiah Arun Kumar 
Published: October 2023

Battery Management System (BMS) functions to monitor individual cell in a battery pack and its crucial task is to maintain stability throughout the battery pack. The BMS is responsible for maintaining the safety of the battery as well as not to harm the user or environment. The parameters that are to be monitored in a battery are Voltage, Current and Temperature. With the collected data, BMS carefully monitors the charging–discharging behavior of the battery particularly in the Lithium-ion (Li-ion) batteries in which charging and discharging behavior are completely different. This paper proposes a real-time IOT connected deep learning algorithm for estimation of State-of-Charge (SoC) of Li-ion batteries. This paper provides unique objectives and congruence between model-based conventional methods and state-of-the-art deep learning algorithm, specifically Feed Forward Neural Network (FNN) which is nonRecurrent. This paper also highlights the advantages of Internet-of-Things (IoT) connected deep learning algorithm for estimation of State-of-Charge of Li-ion batteries in Hybrid Electric Vehicles (HEVs) and Electric Vehicles (EVs). The major advantage of the proposed method is that the Artificial Intelligence (AI)-based techniques aim to bring the estimation error less than 2% at a low cost and time without the model of the battery, at par with conventional method of Extended Kalman Filter (EKF) which is the best ever practical estimation theory. Another advantage of the proposed method is that in an abnormal condition (i.e., Unsafe Temperature) the IF This Then That (IFTTT) IoT mobile application interfaced with BMS through ThingSpeak cloud, sends a notification alert to the battery expert or to the user prior to an emergency. Finally, the real-time data of the battery parameters are collected through ThingSpeak cloud platform for future research and analysis.
Comparison between effects of instrument-assisted soft tissue mobilization and manual myofascial release on pain, range of motion and function in myofascial pain syndrome of upper trapezius — A randomized controlled trial
Authors: Agarwal Shweta , Bedekar Nilima , Shyam Ashok , Sancheti Parag 
Published: October 2023

Background: Myofascial pain syndrome (MPS) is a muscle pain disorder characterized by the presence of Myofascial Trigger Point (MTrP) within a taut band, local tenderness, referral of pain to a distant site, restricted range of motion, and autonomic phenomena. The upper trapezius is the muscle most often affected by MTrPs. Manual myofascial release (MFR) and Instrument-Assisted Soft Tissue Mobilization (IASTM) are techniques of soft tissue release that are used to resolve MPS. Fifty six percent of physiotherapists complain of pain in multiple areas due to the massage and manual therapy that they have to perform. Objective: The objective of this study is to find whether IASTM is better than manual MFR in treating patients with MPS in upper trapezius. Methods: This study was a single-blinded randomized controlled trial that included 31 participants, both males and females between the age groups of 18–50 years. Participants were randomly divided into two groups. Three sessions were given over a period of one week for both groups. Group A received IASTM along with conventional treatment and Group B received Manual MFR along with the conventional treatment. The outcome measures evaluated were pain, cervical range of motion, pain pressure threshold (PPT) of trigger points, and the neck disability index. Pre- and post-measurements were taken and the analysis was done. Results: Both the treatment methods significantly reduced pain, improved PPT, range of motion, and function. The effects between the groups showed that IASTM was significantly better than manual MFR to reduce pain. The improvement in PPT, range of motion and function were equal in both the groups. Conclusion: IASTM and manual MFR both are effective individually as treatment procedures for pain, PPT, range of motion, and function. Neither of the treatment options can be considered better that the other. The clinician can decide based on the availability of the instrument, training, patient’s preference, and his/her comfort whether which of the two treatment methods should be used.
KiT-RT: An Extendable Framework for Radiative Transfer and Therapy
Authors: Kusch Jonas , Schotthöfer Steffen , Stammer Pia , Wolters Jannick , Xiao Tianbai 
Published: October 2023

In this article, we present Kinetic Transport Solver for Radiation Therapy (KiT-RT), an open source C++-based framework for solving kinetic equations in therapy applications available at
https://github.com/CSMMLab/KiT-RT
. This software framework aims to provide a collection of classical deterministic solvers for unstructured meshes that allow for easy extendability. Therefore, KiT-RT is a convenient base to test new numerical methods in various applications and compare them against conventional solvers. The implementation includes spherical harmonics, minimal entropy, neural minimal entropy, and discrete ordinates methods. Solution characteristics and efficiency are presented through several test cases ranging from radiation transport to electron radiation therapy. Due to the variety of included numerical methods and easy extendability, the presented open source code is attractive for both developers, who want a basis to build their numerical solvers, and users or application engineers, who want to gain experimental insights without directly interfering with the codebase.
Symphony: Orchestrating Sparse and Dense Tensors with Hierarchical Heterogeneous Processing
Authors: Pellauer Michael , Clemons Jason , Balaji Vignesh , Crago Neal , Jaleel Aamer , Lee Donghyuk , O’Connor Mike , Parashar Angshuman , Treichler Sean , Tsai Po-An , Keckler Stephen W. , Emer Joel S. 
Published: October 2023

Sparse tensor algorithms are becoming widespread, particularly in the domains of deep learning, graph and data analytics, and scientific computing. Current high-performance broad-domain architectures, such as GPUs, often suffer memory system inefficiencies by moving too much data or moving it too far through the memory hierarchy. To increase performance and efficiency, proposed domain-specific accelerators tailor their architectures to the data needs of a narrow application domain, but as a result cannot be applied to a wide range of algorithms or applications that contain a mix of sparse and dense algorithms.
This article proposes Symphony, a hybrid programmable/specialized architecture that focuses on the orchestration of data throughout the memory hierarchy to simultaneously reduce the movement of unnecessary data and data movement distances. Key elements of the Symphony architecture include (1) specialized reconfigurable units aimed not only at roofline floating-point computations but also at supporting data orchestration features, such as address generation, data filtering, and sparse metadata processing; and (2) distribution of computation resources (both programmable and specialized) throughout the on-chip memory hierarchy. We demonstrate that Symphony can match non-programmable ASIC performance on sparse tensor algebra and provide 31× improved runtime and 44× improved energy over a comparably provisioned GPU for these applications.
SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials
Authors: Conte Benedetta , Boni Luca , Bisagni Giancarlo , Durando Antonio , Sanna Giovanni , Gori Stefania , Garrone Ornella , Tamberi Stefano , De Placido Sabino , Schettini Francesco , Pazzola Antonio , Ponzone Riccardo , Montemurro Filippo , Lunardi Gianluigi , Notaro Rosario , De Angioletti Maria , Turletti Anna , Mansutti Mauro , Puglisi Fabio , Frassoldati Antonio , Porpiglia Mauro , Fabi Alessandra , Generali Daniele , Scognamiglio Giovanni , Rossi Maura , Brasó-Maristany Fara , Prat Aleix , Cardinali Barbara , Piccioli Patrizia , Serra Martina , Lastraioli Sonia , Bighin Claudia , Poggio Francesca , Lambertini Matteo , Del Mastro Lucia 
Published: October 2023

Abstract

Purpose:
In estrogen receptor–positive (ER+) breast cancer, single-nucleotide polymorphisms (SNP) in the aromatase gene might affect aromatase inhibitors (AI) metabolism and efficacy. Here, we assessed the impact of SNP on prognosis and toxicity of patients receiving adjuvant letrozole.

Experimental Design:
We enrolled 886 postmenopausal patients in the study. They were treated with letrozole for 2 to 5 years after taking tamoxifen for 2 to 6 years, continuing until they completed 5 to 10 years of therapy. Germline DNA was genotyped for SNP rs4646, rs10046, rs749292, and rs727479. Log-rank test and Cox model were used for disease-free survival (DFS) and overall survival (OS). Cumulative incidence (CI) of breast cancer metastasis was assessed through competing risk analysis, with contralateral breast cancer, second malignancies and non-breast cancer death as competing events. CI of skeletal and cardiovascular events were assessed using DFS events as competing events. Subdistribution HR (sHR) with 95% confidence intervals were calculated through Fine-Gray method.

Results:
No SNP was associated with DFS. Variants rs10046 [sHR 2.03, (1.04–2.94)], rs749292 [sHR 2.11, (1.12–3.94)], and rs727479 [sHR 2.62, (1.17–5.83)] were associated with breast cancer metastasis. Three groups were identified on the basis of the number of these variants (0, 1, &gt;1). Variant-based groups were associated with breast cancer metastasis (10-year CI 2.5%, 7.6%, 10.7%, P = 0.035) and OS (10-year estimates 96.5%, 93.0%, 89.6%, P = 0.030). Co-occurrence of rs10046 and rs749292 was negatively associated with 10-year CI of skeletal events (3.2% vs. 10%, P = 0.033). A similar association emerged between rs727479 and cardiovascular events (0.3% vs. 2.1%, P = 0.026).

Conclusions:
SNP of aromatase gene predict risk of metastasis and AI-related toxicity in ER+ early breast cancer, opening an opportunity for better treatment individualization.