bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Biological Modeling Identifies PD-(L)1 Immunotherapy Sensitivity Among Molecular Subgroups of KRAS-Mutated Non–Small-Cell Lung Cancer
Authors: Padda Sukhmani K. , Aredo Jacqueline V. , Vali Shireen , Singh Neeraj K. , Vasista Sumanth M. , Kumar Ansu , Neal Joel W. , Abbasi Taher , Wakelee Heather A. 
Published: January 2021

PURPOSE KRAS-mutated ( KRASMUT) non–small-cell lung cancer (NSCLC) is emerging as a heterogeneous disease defined by comutations, which may confer differential benefit to PD-(L)1 immunotherapy. In this study, we leveraged computational biological modeling (CBM) of tumor genomic data to identify PD-(L)1 immunotherapy sensitivity among KRASMUT NSCLC molecular subgroups. MATERIALS AND METHODS In this multicohort retrospective analysis, the genotype clustering frequency ranked method was used for molecular clustering of tumor genomic data from 776 patients with KRASMUT NSCLC. These genomic data were input into the CBM, in which customized protein networks were characterized for each tumor. The CBM evaluated sensitivity to PD-(L)1 immunotherapy using three metrics: programmed death-ligand 1 expression, dendritic cell infiltration index (nine chemokine markers), and immunosuppressive biomarker expression index (14 markers). RESULTS Genotype clustering identified eight molecular subgroups and the CBM characterized their shared cancer pathway characteristics: KRAS MUT/ TP53 MUT, KRAS MUT/ CDKN2A/ B/ C MUT, KRAS MUT/ STK11 MUT, KRAS MUT/ KEAP1 MUT, KRAS MUT/ STK11 MUT/ KEAP1 MUT, KRAS MUT/ PIK3CA MUT, KRAS MUT/ ATM MUT, and KRAS MUT without comutation. CBM identified PD-(L)1 immunotherapy sensitivity in the KRAS MUT/ TP53 MUT, KRAS MUT/ PIK3CA MUT, and KRAS MUT alone subgroups and resistance in the KEAP1 MUT containing subgroups. There was insufficient genomic information to elucidate PD-(L)1 immunotherapy sensitivity by the CBM in the KRAS MUT/ CDKN2A/ B/ C MUT, KRAS MUT/ STK11 MUT, and KRAS MUT/ ATM MUT subgroups. In an exploratory clinical cohort of 34 patients with advanced KRASMUT NSCLC treated with PD-(L)1 immunotherapy, the CBM-assessed overall survival correlated well with actual overall survival ( r = 0.80, P < .001). CONCLUSION CBM identified distinct PD-(L)1 immunotherapy sensitivity among molecular subgroups of KRASMUT NSCLC, in line with previous literature. These data provide proof-of-concept that computational modeling of tumor genomics could be used to expand on hypotheses from clinical observations of patients receiving PD-(L)1 immunotherapy and suggest mechanisms that underlie PD-(L)1 immunotherapy sensitivity.
Effects of variable oxygen regimes on mitochondrial bioenergetics and reactive oxygen species production in a marine bivalve, Mya arenaria
Authors: Ouillon Natascha , Sokolov Eugene P. , Otto Stefan , Rehder Gregor , Sokolova Inna M. 
Published: January 2021

ABSTRACT
Estuarine and coastal benthic organisms often experience fluctuations in oxygen levels that can negatively impact their mitochondrial function and aerobic metabolism. To study these impacts, we exposed a common sediment-dwelling bivalve, the soft-shell clam Mya arenaria, for 21 days to chronic hypoxia (PO2 ∼4.1 kPa), cyclic hypoxia (PO2 ∼12.7–1.9 kPa, mean 5.7 kPa) or normoxia (PO2 ∼21.1 kPa). pH was manipulated to mimic the covariation in CO2/pH and oxygen levels in coastal hypoxic zones. Mitochondrial respiration, including proton leak, the capacity for oxidative phosphorylation (OXPHOS), the maximum activity of the electron transport system (ETS), reactive oxygen species (ROS) production, and activity and oxygen affinity of cytochrome c oxidase (CCO) were assessed. Acclimation to constant hypoxia did not affect the studied mitochondrial traits except for a modest decrease in the OXPHOS coupling efficiency. Cyclic hypoxia had no effect on OXPHOS or ETS capacity, but increased proton leak and lowered mitochondrial OXPHOS coupling efficiency. Furthermore, mitochondria of clams acclimated to cyclic hypoxia had higher rates of ROS generation compared with the clams acclimated to normoxia or chronic hypoxia. CCO activity was upregulated under cyclic hypoxia, but oxygen affinity of CCO did not change. These findings indicate that long-term cyclic hypoxia has a stronger impact on the mitochondria of M. arenaria than chronic hypoxia and might lead to impaired ATP synthesis, higher costs of mitochondrial maintenance and oxidative stress. These changes might negatively affect populations of M. arenaria in the coastal Baltic Sea under increasing hypoxia pressure.
Ontogeny of the star compass in birds: pied flycatchers (Ficedula hypoleuca) can establish the star compass in spring
Authors: Zolotareva Anna , Utvenko Gleb , Romanova Nadezhda , Pakhomov Alexander , Chernetsov Nikita 
Published: January 2021

ABSTRACT
The star compass of birds, like the sun compass, is not innate. To possess either of them, birds have to observe the rotating sky and determine its centre of rotation (in the case of the star compass) or the sun's movement (for the sun compass). Young birds are believed to learn how to use the star compass before their first migration, even though the evidence of this is lacking. Here, we tested whether hand-raised Pied flycatchers (Ficedula hypoleuca) that had not established the star compass prior to their first autumn migration can gain it later in their ontogeny, in spring. We also attempted to examine whether the observation of diurnal celestial cues (the sun and polarized light) prior to autumn migration would affect the process of star compass learning in spring. When tested in the vertical magnetic field under the natural starry sky, the group of birds that observed the stars in spring as the first celestial cues were able to choose the migratory direction. In contrast, the birds that had never seen the stars were not able to use the nightly celestial cues in the vertical magnetic field. However, birds that had seen the daytime celestial cues till autumn and the stars at spring were disoriented, although this might be due to the small sample size. Our data suggest the possibility that the star compass may be learned in spring and emphasize the necessity for further research into the interaction of celestial compasses.
Volumetric Modulated Arc Therapy (VMAT): A modern radiotherapy technique - A single institutional experience
Authors: Rashid Azhar , Ahmed Zaeem , Memom Muhammad Ali , Hashim Abdul Sattar M 
Published: January 2021

Objective: To evaluate VMAT plans for conformity and homogeneity of radiation dose to the target in order to share our experience as a pioneering institute to use VMAT technology in Pakistan.
Methods: Since December 2014 to January 2018, 530 patients of various anatomical sites were treated by VMAT technique at Neurospinal Cancer Care Institute (NCCI) Karachi Pakistan. ERGO++ planning system (Version 1.7.2) was used to develop VMAT plans with single or multiple arcs by the rotation of couch and gantry. The plans were evaluated by calculating Conformity Index (CI) and Homogeneity Index (HI) and critical organ (OARs) doses of individual tumor sites.
Results: The average CI of various sites was 1.4 (range: 1.0–2.0) and average HI of various sites was 1.20 (range: 1.07–1.374), respective critical organ doses were adequately achieved.
Conclusions: VMAT treatment planning technique showed good conformal and homogeneous target coverage with sparing of organs at risk and reduced treatment delivery time. With these features, safety of VMAT technique may allow its routine clinical use, though it is still under investigation in many areas.
Abbreviations Used:CI: Conformity Index, HI: Homogeneity Index, GI: Gradient Index, SIB: Simultaneous Integrated Boost, SRS: Stereotactic Radiosurgery, SBRT: Stereotactic Body Radiotherapy, VMAT: Volumetric Modulated Arc Therapy, MLCs: Multi-leaf Collimators, MU: Monitor Units, DAM: Dynamic Arc module, TV: Target Volume, MD: Maximum Dose, PD: Prescription Dose, RTOG: Radiation Therapy Oncology Group, Linac: Linear accelerator.
doi: https://doi.org/10.12669/pjms.37.2.2647
How to cite this:Rashid A, Ahmad Z, Memon MA, Hashim ASM. Volumetric Modulated Arc Therapy (VMAT): A modern radiotherapy technique-A single institutional experience. Pak J Med Sci. 2021;37(2):355-361. doi: https://doi.org/10.12669/pjms.37.2.2647
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A metaftonímia presente na construção X virar Uber
Authors: Palomanes Ribeiro Roza Maria 
Published: January 2021

O presente artigo tem como objeto de estudo a construção X virar Uber. O fenômeno da uberização, crescente no Brasil e que levou desempregados a se cadastrarem como motoristas do aplicativo administrado pela empresa UBER resultou no surgimento da construção em estudo frequente na fala do brasileiro. O propósito da pesquisa é analisar a construção sob o viés teórico da Linguística Cognitiva, mais especificamente no que tange os processamentos metafórico e metonímico (Lakoff e Johnson (2002), Radden e kövecses, (2007), Lakoff e Turner (1989), Croft (1993) e Gossens (2002)). Para tanto, coletaram-se dados através da ferramenta de buscas GOOGLE, levando-se em conta as 100 primeiras ocorrências distribuídas nas 10 primeiras páginas de busca, optando-se por um tratamento qualitativo dos dados. Após seleção e análise dos dados coletados, chega-se à conclusão de que ocorre, neste caso estudado, o fenômeno da metaftonímia do tipo metáfora da metonímia, em que a entidade conceptual Empresa Uber provê acesso mental à entidade conceptual motorista de aplicativo, dentro do mesmo domínio, configurando o processo metonímico. E, ao mesmo tempo, se dá um mapeamento entre domínios da experiência sustentados pela metáfora O HOMEM É UMA ENTIDADE NÃO HUMANA. Espera-se, com a pesquisa, contribuir para os estudos sobre metaftonímia.
A construção de atenuação do discurso com verbo suporte trazer: uma abordagem construcional baseada no uso
Authors: Costa Fábio Rodrigo Gomes da , Machado Vieira Marcia Dos Santos 
Published: January 2021

O presente artigo tem como objetivo analisar a construção de atenuação do discurso, que, no plano da forma, é representada pela estrutura [trazerVsuporte + _____ Elemento não-verbal predicante (com Ndeverbal)]predicador verbal complexo. Esta construção licencia subesquemas construcionais que ou envolvem SN com Ndeverbal ou SP com Ndeverbal no segundo slot, destinado a elemento não-verbal predicante. A construção e seus subesquemas construcionais estão interconectados em uma rede construcional por meio de links taxonômicos, horizontais, sintáticos e lexicais, conforme o modelo de rede proposto por Diessel (2015). As expressões observadas, coletadas no banco de dados do site eletrônico da Assembleia Legislativa do Rio de Janeiro (ALERJ), foram identificadas em discursos de deputados entre os anos de 2011 e 2019. O aparato teórico-metodológico desta análise é a Linguística Funcional-Cognitiva e da Gramática de Construções Baseada no Uso (GCBU). Da análise de dados, destacam-se estes resultados: (i) o preenchimento de elemento não-verbal por SN com Ndeverbal viabiliza moldar o participante sujeito (que pode coincidir ou não com o enunciador) na figura de um porta-voz e (ii) seu preenchimento por SP com Ndeverbal viabiliza sobressair o papel do interlocutor no estado de coisas encaminhado pelo enunciador.
The effect of geriatric comanagement (GC) in geriatric trauma patients treated in a level 1 trauma setting: A comparison of data before and after the implementation of a certified geriatric trauma center
Authors: Halvachizadeh Sascha , Gröbli Lea , Berk Till , Jensen Kai Oliver , Hierholzer Christian , Bischoff-Ferrari Heike A. , Pfeifer Roman , Pape Hans-Christoph 
Published: January 2021

Introduction
Improvements in life expectancy imply that an increase of geriatric trauma patients occurs. These patients require special attention due to their multiple comorbidity issues. The aim of this study was to assess the impact of the implementation of geriatric comanagement (GC) on the allocation and clinical outcome of geriatric trauma patients.

Methods
This observational cohort study aims to compare the demographic development and the clinical outcome in geriatric trauma patients (aged 70 years and older) before and after implementation of a certified geriatric trauma center (GC). Geriatric trauma patients admitted between January 1, 2010 and December 31, 2010 were stratified to group pre-GC and admissions between January 1, 2018 and December 31, 2018 to Group post-GC. We excluded patients requiring end-of-life treatment and those who died within 24 h or due to severe traumatic brain injury. Outcome parameters included demographic changes, medical complexity (measured by American Society of Anaesthesiology Score (ASA) and Charlson Comorbidity Index (CCI)), in-hospital mortality and length of hospitalization.

Results
This study includes 626 patients in Group pre-GC (mean age 80.3 ± 6.7 years) and 841 patients in Group post-GC (mean age 81.1 ± 7.3 years). Group pre-GC included 244 (39.0%) males, group post-GC included 361 (42.9%) males. The mean CCI was 4.7 (± 1.8) points in pre-GC and 5.1 (± 2.0) points in post-GC (p <0.001). In Group pre-GC, 100 patients (16.0%) were stratified as ASA 1 compared with 47 patients (5.6%) in Group post-GC (p <0.001). Group pre-GC had significantly less patients stratified as ASA 3 or higher (n = 235, 37.5%) compared with Group post-GC (n = 389, 46.3%, p <0.001). Length of stay (LOS) decreased significantly from 10.4 (± 20.3) days in Group pre-GC to 7.9 (±22.9) days in Group post-GC (p = 0.011). The 30-day mortality rate was comparable amongst these groups (pre-GC 8.8% vs. post-GC 8.9%).

Conclusion
This study appears to support the implementation of a geriatric trauma center, as certain improvements in the patient care were found: Despite a higher CCI and a higher number of patients with higher ASA classifications, Hospital LOS, complication rates and mortality did were not increased after implementation of the CG. The increase in the case numbers supports the fact that a higher degree of specialization leads to a response by admitting physicians, as it exceeded the expectable trend of demographic ageing. We feel that a larger data base, hopefully in a multi center set up should be undertaken to verify these results.
Evaluation of vessel density in disorganization of retinal inner layers after resolved diabetic macular edema using optical coherence tomography angiography
Authors: Cennamo Gilda , Montorio Daniela , Fossataro Federica , Fossataro Claudia , Tranfa Fausto 
Published: January 2021

PurposeTo evaluate the retinal vessel density (VD) in the macular region and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with and without disorganization of retinal inner layers (DRILs) after resolution of diabetic macular edema.MethodsThirty-seven eyes of 37 DRIL patients (mean age 63 ± 13.97 years), 30 eyes of 30 no DRIL patients and 35 eyes of 35 controls were enrolled in this study. We evaluated the VD in the macular region of superficial capillary plexus (SCP), deep capillary plexus (DCP) and FAZ area.ResultsDRIL and no DRIL groups showed decreased VD in SCP and DCP (p<0.05) and a larger FAZ area (p<0.001) compared to controls. However, DRIL patients revealed a statistically significant reduction in VD of SCP (p = 0.041) and a greater FAZ area (p<0.001) with respect to no DRIL patients. We found a significant negative correlation between the VD of the foveal SCP (r = -0.414, p = 0.011), foveal DCP (r = -0.358, p = 0.025) and best corrected visual acuity (BCVA) in DRIL group. Moreover there was a significant positive correlation between the FAZ area (r = 0.425, p = 0.034) and BCVA. Therefore, in presence of DRILs lower VD values of SCP and DCP and a larger FAZ area correlated with a worse visual acuity. In no DRILs group, there was a significant negative correlation between the VD of the foveal DCP and BCVA.ConclusionOCTA highlights the role of retinal vascular ischemia in the pathogenesis of DRILs. This parameter could represent an important functional predictive factor in diabetic patients.
Choosing important health outcomes for comparative effectiveness research: 6th annual update to a systematic review of core outcome sets for research
Authors: Gargon Elizabeth , Gorst Sarah L. , Matvienko-Sikar Karen , Williamson Paula R. 
Published: January 2021

Background
An annual update to a systematic review of core outcome sets (COS) for research ensures that the COMET database is up-to-date. The aims of this study were to: (i) identify COS that were published or indexed in 2019 and to describe the methodological approaches used in these studies; (ii) investigate whether children have been included as participants in published COS development studies, and which methods have been used to facilitate their participation; iii) update a previous exercise to identify COS relevant to the most burdensome global diseases and injuries.

Methods
MEDLINE and SCOPUS were searched to identify studies published or indexed between (and inclusive of) January 2019 and December 2019. Automated screening methods were used to rank the citations in order of relevance; the top 25% in ranked priority order were screened for eligibility. COS were assessed against each of the Core Outcome Set-STAndards for Development (COS-STAD). A search of the COMET database was undertaken to identify COS relevant to the 25 leading causes of disease burden.

Results
Thirty-three studies, describing the development of 37 COS, were included in this update. These studies have been added to the COMET database, which now contains 370 published (1981–2019) COS studies for clinical research. Six (18%) of the 33 studies in this update were deemed to have met all of the minimum standards for COS development (range = 4 to 12 criteria, median = 9 criteria). Of the 370 COS studies published to date, 82 COS have been developed for paediatric health conditions and children would have been eligible to participate in 68/82 of these studies. Eleven of these 68 (16%) COS studies have included children as participants within the development process, most commonly through participation in Delphi surveys. Relevant COS were identified for 22/25 leading causes of global disease burden.

Conclusion
There has been a demonstrated increase in COS developed for both research and routine practice, and consistently high inclusion of patient participants. COS developed for paediatric conditions need to further incorporate the perspectives of children, alongside parents and other adults, and adopt research methods fit for this purpose. COS developers should consider the gaps identified in this update as priorities for COS development.
Process evaluation of enhancing primary health care for non-communicable disease management in Malaysia: Uncovering the fidelity & feasibility elements
Authors: Low Lee Lan , A. B. Rahim Fathullah Iqbal , Hamzah Nur Aqlili Riana , Ismail Mohd Safiee 
Published: January 2021

Background
In combating the increasing trend of non-communicable diseases (NCDs) over the last two decades in the country, the Ministry of Health Malaysia developed the Enhanced Primary Health Care (EnPHC) initiative to improve care management across different levels of the public service delivery network. An evaluation research component was embedded to explore the implementation issues in terms of fidelity, feasibility, adaptation and benefit of the initiative’s components which were triage, care coordination, screening, risk management and referral system.

Methods
A mixed methods study was conducted at 20 participating EnPHC clinics in Johor and Selangor, two months after the intervention was initiated. Data collected from self-reported forms and a structured observation checklist were descriptively analysed. In-depth interviews were also conducted with 20 participants across the clinics selected to clarify any information gaps observed in each clinic, and data were thematically analysed.

Results
Evaluation showed that all components of EnPHC intervention had been successfully implemented except for the primary triage counter and visit checklist. The challenges were mainly discovered in terms of human resource and physical structure. Although human resource was a common implementation challenge across all interventions, clinic-specific issues could still be identified. Among the adaptive measures taken were task sharing among staff and workflow modification to match the clinic’s capacity. Despite the challenges, early benefits of implementation were highlighted especially in terms of service outcomes.

Conclusions
The evaluation study disclosed issues of human resource and physical infrastructure when a supplementary intervention is implemented. To successfully achieve a scaled-up PHC service delivery model based on comprehensive management of NCDs patient-centred care, the adaptive measures in local clinic context highlight the importance of collaboration between good organisational process and good clinical practice and process.
Twin pregnancy and perinatal outcomes: Data from ‘Birth in Brazil Study’
Authors: Esteves-Pereira Ana Paula , da Cunha Antônio José Ledo Alves , Nakamura-Pereira Marcos , Moreira Maria Elisabeth , Domingues Rosa Maria soares madeira , Viellas Elaine Fernandes , Leal Maria do Carmo , Granado nogueira da Gama Silvana 
Published: January 2021

Background
Twin pregnancies account for 0.5–2.0% of all gestations worldwide. They have a negative impact on perinatal health indicators, mainly owing to the increased risk for preterm birth. However, population-based data from low/middle income countries are limited. The current paper aims to understand the health risks of twins, compared to singletons, amongst late preterms and early terms.

Methods
Data is from “Birth in Brazil”, a national inquiry into childbirth care conducted in 2011/2012 in 266 maternity hospitals. We included women with a live birth or a stillborn, and excluded births of triplets or more, totalling 23,746 singletons and 554 twins. We used multiple logistic regressions and adjusted for potential confounders.

Results
Twins accounted for 1.2% of gestations and 2.3% of newborns. They had higher prevalence of low birth weight and intrauterine growth restriction, when compared to singletons, in all gestational age groups, except in the very premature ones (<34 weeks). Amongst late preterm’s, twins had higher odds of jaundice (OR 2.7, 95% CI 1.8–4.2) and antibiotic use (OR 1.8, 95% CI 1.1–3.2). Amongst early-terms, twins had higher odds of oxygen therapy (OR 2.7, 95% CI 1.3–5.9), admission to neonatal intensive care unit (OR 3.1, 95% CI 1.5–6.5), transient tachypnoea (OR 3.7, 95% CI 1.5–9.2), jaundice (OR 2.8, 95% CI 1.3–5.9) and antibiotic use (OR 2.2, 95% CI 1.14.9). In relation to birth order, the second-born infant had an elevated likelihood of jaundice, antibiotic use and oxygen therapy, than the first-born infant.

Conclusion
Although strongly mediated by gestational age, an independent risk remains for twins for most neonatal morbidities, when compared to singletons. These disadvantages seem to be more prominent in early-term newborns than in the late preterm ones.