bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of a deep reinforcement learning network for dose-volume-constrained treatment planning in prostate cancer intensity modulated radiotherapy
Authors: Sprouts Damon , Gao Yin , Wang Chao , Jia Xun , Shen Chenyang , Chi Yujie 
Published: May 2022

Abstract
Although commercial treatment planning systems (TPSs) can automatically solve the optimization problem for treatment planning, human planners need to define and adjust the planning objectives/constraints to obtain clinically acceptable plans. Such a process is labor-intensive and time-consuming. In this work, we show an end-to-end study to train a deep reinforcement learning (DRL) based virtual treatment planner (VTP) that can behave like a human to operate a dose-volume constrained treatment plan optimization engine following the parameters used in Eclipse TPS for high-quality treatment planning. We considered the prostate cancer IMRT treatment plan as the testbed. The VTP took the dose-volume histogram (DVH) of a plan as input and predicted the optimal strategy for constraint adjustment to improve the plan quality. The training of VTP followed the state-of-the-art Q-learning framework. Experience replay was implemented with epsilon-greedy search to explore the impacts of taking different actions on a large number of automatically generated plans, from which an optimal policy can be learned. Since a major computational cost in training was to solve the plan optimization problem repeatedly, we implemented a graphical processing unit (GPU)-based technique to improve the efficiency by 2-fold. Upon the completion of training, the established VTP was deployed to plan for an independent set of 50 testing patient cases. Connecting the established VTP with the Eclipse workstation via the application programming interface, we tested the performance the VTP in operating Eclipse TPS for automatic treatment planning with another two independent patient cases. Like a human planner, VTP kept adjusting the planning objectives/constraints to improve plan quality until the plan was acceptable or the maximum number of adjustment steps was reached under both scenarios. The generated plans were evaluated using the ProKnow scoring system. The mean plan score (± standard deviation) of the 50 testing cases were improved from 6.18 ± 1.75 to 8.14 ± 1.27 by the VTP, with 9 being the maximal score. As for the two cases under Eclipse dose optimization, the plan scores were improved from 8 to 8.4 and 8.7 respectively by the VTP. These results indicated that the proposed DRL-based VTP was able to operate the in-house dose-volume constrained TPS and Eclipse TPS to automatically generate high-quality treatment plans for prostate cancer IMRT.
Exodus: sequencing-based pipeline for quantification of pooled variants
Authors: Vainberg-Slutskin Ilya , Kowalsman Noga , Silberberg Yael , Cohen Tal , Gold Jenia , Kario Edith , Weiner Iddo , Gahali-Sass Inbar , Kredo-Russo Sharon , Zak Naomi B , Bassan Merav 
Published: May 2022

AbstractSummaryNext-Generation Sequencing is widely used as a tool for identifying and quantifying microorganisms pooled together in either natural or designed samples. However, a prominent obstacle is achieving correct quantification when the pooled microbes are genetically related. In such cases, the outcome mostly depends on the method used for assigning reads to the individual targets. To address this challenge, we have developed Exodus—a reference-based Python algorithm for quantification of genomes, including those that are highly similar, when they are sequenced together in a single mix. To test Exodus’ performance, we generated both empirical and in silico next-generation sequencing data of mixed genomes. When applying Exodus to these data, we observed median error rates varying between 0% and 0.21% as a function of the complexity of the mix. Importantly, no false negatives were recorded, demonstrating that Exodus’ likelihood of missing an existing genome is very low, even if the genome’s relative abundance is low and similar genomes are present in the same mix. Taken together, these data position Exodus as a reliable tool for identifying and quantifying genomes in mixed samples. Exodus is open source and free to use at: https://github.com/ilyavs/exodus.Availability and implementationExodus is implemented in Python within a Snakemake framework. It is available on GitHub alongside a docker containing the required dependencies: https://github.com/ilyavs/exodus. The data underlying this article will be shared on reasonable request to the corresponding author.Supplementary informationSupplementary data are available at Bioinformatics online.
Multivariate Optimization for Determination of Favipiravir, a SARS-CoV-2 Molecule, by the Reverse-Phase Liquid Chromatographic Method Using a QbD Approach
Authors: Nishanth G V V , Spandana Tatineni , Sri Chiriki Devi , Nataraj Varshini , Vikram P R Hemanth , Gurupadayya B M 
Published: May 2022

Abstract
The object of the analytical work is to develop an analytical multivariate optimization for the determination of Favipiravir (FAV), a SARS-CoV-2 molecule, by the reverse-phase liquid chromatographic method using the analytical quality by design approach. FAV is used as an antiviral drug. Box-Behnken design is utilized for the optimization of the experiment and to identify the critical method parameters like the volume of acetonitrile, temperature and flow rate. Further, these factors are used to design the suitable mathematical models and illustrate their effect on various responses. This newly developed method utilized C18 column (5μm, 100 × 4.6 mm) and a temperature of 40°C with a flow rate of 0.5 mL/min. The mobile phase is composed of acetonitrile and ammonium acetate buffer (pH 4), in the ratio of 20:80v/v and the wavelength of HPLC UV-Detector was fixed to 323nm. This method is validated according to International Council for Harmonization Q2 (R1) guidelines. The System suitability is performed and the retention time of Favipiravir is 3.4min. The linearity range is obtained at 0.062 – 4 μg/mL with a correlation coefficient (r2 = 0.9979). The recovery is found to be in the range of 98.84–100%. Thus, the intended method is found to be simple and robust.
Bridging Fixed Dose to Body Weight-based Regimen of Adalimumab in Paediatric Ulcerative Colitis Using a Pharmacometric Modelling Approach: Case Study with the Phase 3 ENVISION I Trial
Authors: Stodtmann Sven , Chen Mong-Jen , Siovitz Lucia , Bereswill Mareike , Lazar Andreas , Croft Nicholas , Kierkus Jaroslaw , Faubion William A , Mostafa Nael M 
Published: May 2022

Abstract

Background and Aims
The Phase 3 study ENVISION I demonstrated efficacy and safety of adalimumab in paediatric patients with moderate to severe ulcerative colitis. The protocol-specified high-dose adalimumab regimen was numerically more efficacious than the standard-dose regimen. The objective of this work was to bridge a fixed-dosing regimen to the protocol-specified high-induction/high-maintenance, body weight-based dosing regimen studied in ENVISION I, using a pharmacometrics modelling and simulation approach.

Methods
A stepwise strategy was implemented, including developing an adalimumab paediatric population pharmacokinetic model; using this model to determine a fixed-dosing regimen in paediatric ulcerative colitis patients which achieves similar concentrations to those observed in ENVISION I patients; determining adalimumab exposure-response relationship using population pharmacokinetic/pharmacodynamic model and data from ENVISION I; simulating clinical remission rate in paediatric ulcerative colitis patients using the Markov exposure-response model and the dosing regimen determined to provide similar efficacy to that observed in ENVISION I.

Results
Both developed population pharmacokinetic and pharmacokinetic/pharmacodynamic models adequately described the observed data. Adalimumab exposure was identified as a significant predictor of clinical remission at Week 8 based on logistic regression [p &lt;0.01]. Simulated efficacy suggested that the fixed-dosing regimen performs similarly to the more efficacious dosing regimen used in ENVISION I, by providing comparable clinical remission per Partial Mayo Score response rates over time. No relationship between adalimumab exposure and adverse events was identified.

Conclusions
The population pharmacokinetic/pharmacodynamic model supports the appropriateness of the use of the fixed-dosing regimen in the paediatric ulcerative colitis population.
Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy
Authors: Joseph Philip , Kutty Vellappillil Raman , Mohan Viswanathan , Kumar Rajesh , Mony Prem , Vijayakumar Krishnapillai , Islam Shofiqul , Iqbal Romaina , Kazmi Khawar , Rahman Omar , Yusuf Rita , Anjana Ranjit Mohan , Mohan Indu , Rangarajan Sumathy , Gupta Rajeev , Yusuf Salim 
Published: May 2022

Abstract

Aim
To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia.

Methods and results
Prospective study of 33 583 individuals 35–70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%).

Conclusion
In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants.
Systemic Inflammation Is Associated With Future Risk of Fatal Infection: An Observational Cohort Study
Authors: Drozd Michael , Pujades-Rodriguez Mar , Morgan Ann W , Lillie Patrick J , Witte Klaus K , Kearney Mark T , Cubbon Richard M 
Published: May 2022

Abstract

Background
Many diseases are associated with chronic inflammation, resulting in widening application of anti-inflammatory therapies. Although they are effective as disease-modifying agents, these anti-inflammatory therapies increase the risk of serious infection; however, it remains unknown whether chronic systemic inflammation per se is also associated with fatal infection.

Methods
Using serum C-reactive protein (CRP) data from 461 052 UK Biobank participants, we defined incidence rate ratios (IRRs) for death from infection, cardiovascular disease, or other causes and adjusted for comorbidities and the use of anti-inflammatory therapies.

Results
Systemic inflammation, defined as CRP ≥2 mg/L, was common in all comorbidities considered. After adjusting for confounding factors, systemic inflammation was associated with a higher IRR point estimate for infection death (1.70; 95% confidence interval [CI], 1.51–1.92) than cardiovascular (1.48; CI, 1.40–1.57) or other death (1.41; CI, 1.37–1.45), although CIs overlapped. C-reactive protein thresholds of ≥5 and ≥10 mg/L yielded similar findings, as did analyses in people with ≥2, but not &lt;2, comorbidities.

Conclusions
Systemic inflammation per se identifies people at increased risk of infection death, potentially contributing to the observed risks of anti-inflammatory therapies in clinical trials. In future clinical trials of anti-inflammatory therapies, researchers should carefully consider risks and benefits in target populations, guided by research into mechanisms of infection risk.
Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 Coronavirus Efficacy (COVE) Trial
Authors: El Sahly Hana M , Baden Lindsey R , Essink Brandon , Montefiori David , McDermont Adrian , Rupp Richard , Lewis Michael , Swaminathan Shobha , Griffin Carl , Fragoso Veronica , Miller Vicki E , Girard Bethany , Paila Yamuna D , Deng Weiping , Tomassini Joanne E , Paris Robert , Schödel Florian , Das Rituparna , August Allison , Leav Brett , Miller Jacqueline M , Zhou Honghong , Pajon Rolando ,   for the Coronavirus Efficacy (COVE) Study Group
Published: May 2022

Abstract

Background
Messenger RNA (mRNA)–1273 vaccine demonstrated 93.2% efficacy against coronavirus disease 2019 (COVID-19) in the Coronavirus Efficacy (COVE) trial. The humoral immunogenicity results are now reported.

Methods
Participants received 2 mRNA-1273 (100 µg) or placebo injections, 28 days apart. Immune responses were evaluated in a prespecified, randomly selected per-protocol immunogenicity population (n = 272 placebo; n = 1185 mRNA-1273). Serum binding antibodies (bAbs) and neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–spike protein were assessed at days 1, 29, and 57 by baseline SARS-CoV-2–negative (n = 1197) and SARS-CoV-2–positive (n = 260) status, age, and sex.

Results
SARS-CoV-2–negative vaccinees had bAb geometric mean AU/mL levels of 35 753 at day 29 that increased to 316 448 at day 57 and nAb inhibitory dilution 50% titers of 55 at day 29 that rose to 1081 at day 57. In SARS-CoV-2–positive vacinees, the first mRNA-1273 injection elicited bAb and nAb levels that were 11-fold (410 049) and 27-fold (1479) higher than in SARS-CoV-2–negative vaccinees, respectively, and were comparable to levels after 2 injections in uninfected participants. Findings were generally consistent by age and sex.

Conclusions
mRNA-1273 elicited robust serologic immune responses across age, sex, and SARS-CoV-2 status, consistent with its high COVID-19 efficacy. Higher immune responses in those previously infected support a booster-type effect.
Clinical Trials Registration. NCT04470427.
Socio-economic inequalities in intimate partner violence justification among women in Ghana: analysis of the 2014 Ghana Demographic and Health Survey data
Authors: Adu Collins 
Published: May 2022

AbstractBackgroundOne of the key reasons for the high prevalence of intimate partner violence among women is the justification of intimate partner violence. Socio-economic status of women plays a key role in intimate partner violence justification. This study investigated the socio-economic inequalities in the justification of intimate partner violence among Ghanaian women.MethodsData from the 2014 Ghana Demographic and Health Survey were used in this study. The study involved a total of 9267 women. A binary logistic regression analysis was performed to examine the socio-economic disparities in intimate partner violence justification. The findings were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs) demonstrating precision. Statistical significance was set at p&lt;0.05.ResultsThe prevalence of intimate partner violence justification among women in Ghana was 28.2%. Compared with women with no formal of education, those with a higher level of education (aOR 0.17 [95% CI 0.10 to 0.30]) were less likely to justify intimate partner violence. In terms of wealth status, women in the richest quintile had lower odds of justifying intimate partner violence compared with women in the poorest wealth quintile (aOR 0.44 [95% CI 0.28 to 0.67]).ConclusionsInterventions, policies, strategies and programs such as women's equitable access to formal education, formation of stronger social networks to improve women's socio-economic status, advocacy to stop intimate partner violence and empowerment interventions among women should be focused toward contextualizing intimate partner violence in terms of the acceptance of this behaviour, since this can play a significant role in victimization and perpetration.
Computational analysis of metal transfer mode, dynamics, and heat transfer under different pulsating frequencies in pulsed wire-arc additive manufacturing
Authors: Ikram Adeel , Chung Hyun 
Published: May 2022

Abstract
A numerical model of the metal transfer process was developed using the thermomagnetohydrodynamic equations and the phase-field method to investigate the influence of pulse frequency on the metal transfer mode, dynamics, and thermal behavior in the pulsed wire-arc additive manufacturing (WAAM) process. The control of droplet transfer mode, dynamics, and thermal behavior is essential in WAAM; otherwise, several potential defects such as high residual stresses and distortion, poor dimensional accuracy, and surface quality may occur due to uneven heat input condition and process instability. Therefore, in this study, eight sets of pulse frequencies ranging from 50 to 225 Hz, in steps of 25 Hz, using identical power source parameters, such as pulse duty cycle and average current of 25.4% and 152 A, respectively, were considered and compared for a nearly square current waveform. The results reveal that only the current pulses with a medium frequency regime (100–175 Hz) achieve the one-droplet-per-pulse mode of metal transfer. Moreover, an increase in pulse frequency leads to a shorter necking length of the pendent droplet and a significantly lower average speed and temperature of the detached droplet. The results for the heat flux analysis indicate that Joule heating and arc heating decrease due to the increase in pulse frequency, whereas the sheath heating remains almost constant using different pulse frequencies. The proposed numerical scheme provides a detailed understanding of controlling and tailoring the different metal transfer modes and their metal transfer stability during WAAM, which benefits further process optimization and control.
Collective Justice: Ex-Combatants and Community Reparations in Colombia
Authors: Dixon Peter , Firchow Pamina 
Published: May 2022

Abstract
In conflicts involving non-state armed groups, individualized approaches to transitional justice and disarmament, demobilization, and reintegration face significant shortcomings for both victims and ex-combatants. Yet, both transitional justice and disarmament, demobilization, and reintegration have had trouble interrogating the tensions between individualized and collective approaches, focusing more on normative debates over the proper balance than on the actual experiences of communities in transition. This paper seeks to advance this debate through empirical research on the local experience of justice and coexistence amid civilian and ex-combatant communities in Colombia. The authors utilized a unique dataset of ‘everyday’ community-based indicators of coexistence and justice in eight civilian and ex-combatant communities in rural Colombia. Using the country’s web of reparations mechanisms, the paper draws a distinction between ‘state-led’ and ‘community-led’ collective justice and proposes that the latter can speak to both civilian and ex-combatant communities’ priorities and lived experiences—and, ultimately, provide a pathway to coexistence. This would stand in contrast to the Colombian state’s current collective reparations projects by speaking directly to the concerns and priorities of both civilian and ex-combatant communities: on the civilian side, to be compensated directly by those who committed acts of violence; and on the ex-combatant side, to be recognized and accepted as a community. Such a community-led model integrating transitional justice and disarmament, demobilization, and reintegration processes would serve as a pragmatic middle ground between the individual and state-led collective approaches that dominate transitional justice.
Parental Experiences of Adolescent Cancer-Related Pain: A Qualitative Study
Authors: Clews Charlotte , Davis Cara , Loades Maria , Jordan Abbie 
Published: May 2022

Abstract

Objective
Despite advancing medical treatments, pain remains a significant outcome of adolescent cancer, as both a problematic and distressing symptom. With adolescents spending substantial periods of time at home during cancer treatment, parents perceive themselves as central to the experience and management of adolescents’ pain. The present study aimed to explore parental experiences of adolescent cancer-related pain during, and recently after, completing cancer treatment.

Methods
We interviewed 21 parents of adolescents (aged 12–18 years) with cancer, recruited through a hospital in South West England. Interviews were analyzed using reflexive inductive thematic analysis.

Results
Two themes were generated. The first theme, “Parental perceptions of being at the heart of pain management,” focused on the role of parents in adolescents’ pain journeys, and the vast knowledge they gained. The second, “Adapting and readjusting expectations,” captured parents’ journeys in learning to adjust their lives according to adolescents’ pain and difficulties they faced throughout this process.

Conclusions
Findings highlighted parents’ crucial role throughout adolescents’ pain experiences; learning how to manage adolescents’ pain, and supporting them with the detrimental impact on their lives. The findings emphasize the importance of a multidisciplinary approach to supporting families to manage pain. They also indicate a need for targeted research studies investigating parental experiences of adolescent cancer-related pain. This will help professionals understand how best to support parents and adolescents throughout the cancer journey and ultimately improve the physical and psychological outcomes of young people in the longer term.
Granulomatous splenic mass with necrosis revealing an EBV-positive inflammatory follicular dendritic cell sarcoma
Authors: Ungureanu Irena Antonia , Lupinacci Renato Micelli , Parrens Marie , Emile Jean-François 
Published: May 2022

Abstract
Epstein–Barr virus-positive inflammatory follicular dendritic cell sarcoma is a variant of follicular dendritic cell neoplasm most often arising in the liver or spleen. Two histological patterns can be identified in this variant, namely a granulomatous and an eosinophil-rich one. We present the case of a 69-year-old woman with a splenic mass. After being removed, the mass was gray-whitish with an area of necrosis. Histology showed a diffuse distribution of epithelioid granulomas in a background of a dense lymphoplasmacytic infiltrate. Rare atypical cells EBV+ and CD21+ were present in the intergranulomatous areas. Differential diagnosis for the granulomatous type EBV+ inflammatory follicular dendritic cell sarcoma includes infection, sarcoidosis, inflammatory myofibroblastic tumor, T cell lymphoma and vasculitis. The origin of this neoplasm is the follicular dendritic cell, and, due to its similarities with a myofibroblast, differential diagnosis can be challenging. Immunohistochemistry for dendritic markers and in situ hybridization for EBER remain diagnostic keys.