bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional and metabolic remodeling in clear cell renal cell carcinoma caused by ATF4 activation and the integrated stress response (ISR)
Authors: van der Mijn Johannes C. , Chen Qiuying , Laursen Kristian B. , Khani Francesca , Wang Xiaofei , Dorsaint Princesca , Sboner Andrea , Gross Steven S. , Nanus David M. , Gudas Lorraine J. 
Published: June 2022

AbstractResearch has shown extensive metabolic remodeling in clear cell renal cell carcinoma (ccRCC), with increased glutathione (GSH) levels. We hypothesized that activating transcription factor‐4 (ATF4) and the integrated stress response (ISR) induce a metabolic shift, including increased GSH accumulation, and that Vitamin A deficiency (VAD), found in ccRCCs, can also activate ATF4 signaling in the kidney. To determine the role of ATF4, we used publicly available RNA sequencing (RNA‐seq) data sets from The Cancer Genomics Atlas. Subsequently, we performed RNA‐seq and liquid chromatography–mass spectrometry‐based metabolomics analysis of the murine TRAnsgenic Cancer of the Kidney (TRACK) model for early‐stage ccRCC. To validate our findings, we generated RCC4 cell lines with ATF4 gene edits (ATF4‐knockout [KO]) and subjected these cells to metabolic isotope tracing. Analysis of variance, the two‐sided Student's t test, and gene set enrichment analysis were used (p < 0.05) to determine statistical significance. Here we show that most human ccRCC tumors exhibit activation of the transcription factor ATF4. Activation of ATF4 is concomitant with enrichment of the ATF4 gene set and elevated expression of ATF4 target genes ASNS, ALDH1L2, MTHFD2, DDIT3 (CHOP), DDIT4, TRIB3, EIF4EBP1, SLC7A11, and PPP1R15A (GADD34). Transcript profiling and metabolomics analyses show that activated hypoxia‐inducible factor‐1α (HIF1α) signaling in our TRACK ccRCC murine model also induces an ATF4‐mediated ISR. Notably, both normoxic HIF1α signaling in TRACK kidneys and VAD in wild‐type kidneys diminish amino acid levels, increase ASNS, TRIB3, and MTHFD2 messenger RNA levels, and increase levels of lipids and GSH. By metabolic isotope tracing in human RCC4 kidney cancer parental and ATF4 gene‐edited (ATF4‐KO) cell lines, we show that ATF4 increases GSH accumulation in part via activation of the mitochondrial one‐carbon metabolism pathway. Our results demonstrate for the first time that activation of ATF4 enhances GSH accumulation, increases purine and pyrimidine biosynthesis, and contributes to transcriptional and metabolic remodeling in ccRCC. Moreover, constitutive HIF1α expressed only in murine kidney proximal tubules activates ATF4, leading to the metabolic changes associated with the ISR. Our data indicate that HIF1α can promote ccRCC via ATF4 activation. Moreover, lack of Vitamin A in the kidney recapitulates aspects of the ISR.
Predicting the outcome of radiotherapy in brain metastasis by integrating the clinical and MRI‐based deep learning features
Authors: Jalalifar Seyed Ali , Soliman Hany , Sahgal Arjun , Sadeghi‐Naini Ali 
Published: June 2022

AbstractBackgroundA considerable proportion of metastatic brain tumors progress locally despite stereotactic radiation treatment, and it can take months before such local progression is evident on follow‐up imaging. Prediction of radiotherapy outcome in terms of tumor local failure is crucial for these patients and can facilitate treatment adjustments or allow for early salvage therapies.PurposeIn this work, a novel deep learning architecture is introduced to predict the outcome of local control/failure in brain metastasis treated with stereotactic radiation therapy using treatment‐planning magnetic resonance imaging (MRI) and standard clinical attributes.MethodsAt the core of the proposed architecture is an InceptionResentV2 network to extract distinct features from each MRI slice for local outcome prediction. A recurrent or transformer network is integrated into the architecture to incorporate spatial dependencies between MRI slices into the predictive modeling. A visualization method based on prediction difference analysis is coupled with the deep learning model to illustrate how different regions of each lesion on MRI contribute to the model's prediction. The model was trained and optimized using the data acquired from 99 patients (116 lesions) and evaluated on an independent test set of 25 patients (40 lesions).ResultsThe results demonstrate the promising potential of the MRI deep learning features for outcome prediction, outperforming standard clinical variables. The prediction model with only clinical variables demonstrated an area under the receiver operating characteristic curve (AUC) of 0.68. The MRI deep learning models resulted in AUCs in the range of 0.72 to 0.83 depending on the mechanism to integrate information from MRI slices of each lesion. The best prediction performance (AUC = 0.86) was associated with the model that combined the MRI deep learning features with clinical variables and incorporated the inter‐slice dependencies using a long short‐term memory recurrent network. The visualization results highlighted the importance of tumor/lesion margins in local outcome prediction for brain metastasis.ConclusionsThe promising results of this study show the possibility of early prediction of radiotherapy outcome for brain metastasis via deep learning of MRI and clinical attributes at pre‐treatment and encourage future studies on larger groups of patients treated with other radiotherapy modalities.
Development and applicability of a dignity‐centred palliative care programme for people with idiopathic pulmonary fibrosis: A qualitative‐driven mixed methods study
Authors: Igai Yasuko , Porter Sarah E. 
Published: June 2022

AbstractAimsThis study evaluated the acceptability of a dignity‐centred palliative care programme for people with idiopathic pulmonary fibrosis by converging perceptions of living with idiopathic pulmonary fibrosis qualitative data and quantitative data.DesignThe qualitative‐driven mixed methods research addressed the study aim by using a convergent design. This single arm, non‐randomized study used purposive sampling.MethodsInterviews with 12 stable outpatients with IPF provided qualitative data. Their quantitative data were from six scales: self‐esteem, health‐related quality of life, anxiety, depression, dyspnoea, cough and programme satisfaction. Intervention was three educational modules: symptom management, enhancing daily activities and life reviews.ResultsSemi‐structured interviews yielded eight categories. Self‐esteem was not statistically significantly changed. Dyspnoea symptoms improved significantly. Participants (n = 9) holding positive attitudes for living with idiopathic pulmonary fibrosis, had improved lifestyle behaviour and improved or maintained self‐esteem. The meta‐inference regarding idiopathic pulmonary fibrosis perceptions were related to changes in self‐esteem.
EEGcorrelates of quality of life and associations with seizure without awareness and depression in patients with epilepsy
Authors: Azuma Hideki , Akechi Tatsuo 
Published: June 2022

AbstractAimsQuality of life (QOL) is an important issue for not only patients with epilepsy but also physicians. Depression has a large impact on QOL. Nonlinear electroencephalogram (EEG) analysis using machine learning (ML) has the potential to improve the accuracy of the diagnosis of epilepsy. Therefore, in this study, we examined EEG nonlinearity, EEG correlates of QOL in patients with epilepsy, and the accuracy of EEG for the interval from seizure without awareness (SA–) and for depression, using ML.MethodsThe Side Effects and Life Satisfaction (SEALS) inventory was used to assess QOL, and the Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E) was used as a screening tool for depression on the date of the EEG recording. EEG with wavelet denoising (WD), the Savitzky–Golay filter, and non‐denoising were created in combination with low‐ and high‐pass filters. These EEG sets were adopted for phase space reconstruction methods. Using a generalized linear mixed‐effects model for SEALS, sample entropy as a measurement of regularity, SA–, seizure with awareness, and depression were examined.ResultsWD and non‐denoising EEG sets in the bilateral posterior temporal‐occipital, centro‐parietal, parieto‐occipital, and Fz–Cz of the 10–20 method were associated with SEALS and demonstrated nonlinearity, and the moderate effects of classification for the interval elapsed from SA– and for depression. When the intervals from SA– were added, the effects of the EEG classification for depression increased.ConclusionThese findings suggest that EEG regions associated with QOL showing nonlinearity are useful for classifying SA– and depression.
Puberty in pre‐Roman times: A bioarchaeological study of Etruscan‐Samnite adolescents from Pontecagnano (southern Italy)
Authors: Bareggi Alessia , Pellegrino Carmine , Giuffra Valentina , Riccomi Giulia 
Published: June 2022

AbstractObjectivesPuberty is a crucial part of life, representing the biological transition from childhood to adulthood. With the aim of expanding current knowledge of pubertal development and the life course in past populations, this study provides the first investigation of puberty in pre‐Roman Italy.Materials and methodsNine skeletal and dental puberty indicators were assessed in a sample of 84 Etruscan and Samnite individuals (8.0–23.9 years) from Pontecagnano (southern Italy, seventh–fourth centuries BC) to garner insights into the timing and duration of different pubertal stages.ResultsAdolescents from Pontecagnano entered puberty at 10–12 years and completed pubertal development at approximately 20–21 years. Menarche occurred between 14 and 17 years. Remarkable variability in pubertal timing and an overall prolonged pubertal tempo were observed. Unexpectedly, females completed puberty at the same age as males.DiscussionThe onset and completion of puberty in Pontecagnano are mostly in line with pubertal trends emerging from other bioarchaeological studies and historical sources. The considerable inter‐individual variability in pubertal timing seen at the site probably reflects its great sociocultural heterogeneity, whilst the prolonged pubertal tempo could represent an adaptive mechanism in response to environmental disruptors. These may have included endemic diseases characteristic of Pontecagnano's marshy environment and pollutants produced by the Etruscan and Samnite metallurgical industries. Moreover, the role of catch‐up growth in favouring better pregnancy outcomes could explain why female puberty appears particularly stretched. The importance of exploring pubertal development in past societies without culturally biased assumptions is emphasised.
Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma
Authors: Yadgarov Mikhail , Kailash Chaurasiya , Shamanskaya Tatyana , Kachanov Denis , Likar Yury 
Published: June 2022

AbstractBackgroundIn recent years, many research groups have attempted to identify a subgroup of “ultra‐high risk” patients within the high‐risk neuroblastoma (NB) category. The aim of our study was to evaluate the prognostic significance of parameters derived from pretherapeutic 123I‐meta‐iodobenzylguanidine ([123I]mIBG) integrated single photon emission computed tomography and computed tomography in high‐risk patients with NB.MethodsThe established parameters metabolic tumor volume (MTV), maximal standardized uptake value (SUVmax) and the novel parameter tumor asphericity as well as clinical (age, stage) and genetic factors (1p/11q deletions and MYCN amplification) were analyzed in this single‐center retrospective study of high‐risk patients with newly diagnosed NB. Univariate/multivariable Cox regression and propensity score matching were performed for clinical and radiological parameters.ResultsTwenty‐eight high‐risk patients with NB were included (14 males, median age 28.8 (11.3–41.0), range 3–74 months). Multivariable analysis of “full” cohort identified high asphericity (≥65%, adjusted hazard ratio [HR] 5.32, 95% confidence interval [CI]: 1.18–24.07, p = .03) and MTV (≥50 ml, adjusted HR 4.31, 95% CI: 1.18–15.80, p = .027) as the only factors associated with worse event‐free survival. In matched cohort, tumor asphericity was a significant predictor of relapse/progression (HR 3.83, 95% CI: 1.03–14.26, p = .046).ConclusionIn this exploratory study, imaging parameters related to tumor metabolic activity, tumor asphericity and MTV, provided prognostic value for event‐free survival in high‐risk NB patients. Asphericity ≥65% and MTV ≥50 ml may serve as additional prognostic factors to those already used.
Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry
Authors: Rask Olof , Nilsson Fredrik , Lähteenmäki Päivi , Ehrstedt Christoffer , Holm Stefan , Sandström Per‐Erik , Nyman Per , Sabel Magnus , Grillner Pernilla ,   for the Swedish Childhood CNS Tumor Working Group (VCTB)
Published: June 2022

AbstractBackgroundThe elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features.MethodsData prospectively accumulated over a 4‐year period in the Swedish Childhood Cancer Registry from patients aged 0–18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%).ResultsThe time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4‐year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis.ConclusionThis study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.
Preoperative electrodiagnostic planning for upper limb peripheral nerve transfers in cervical spinal cord injury: A narrative review
Authors: Silverman Jordan , Dengler Jana , Song Cimon , Robinson Lawrence R. 
Published: June 2022

AbstractPeripheral nerve transfer (PNT) to improve upper limb function following cervical spinal cord injury (SCI) involves the transfer of supralesional donor nerves under voluntary control to intralesional or sublesional lower motor neurons not under voluntary control. Appropriate selection of donor and recipient nerves and surgical timing affect functional outcomes. Although the gold standard of nerve selection is intraoperative nerve stimulation, preoperative electrodiagnostic (EDX) evaluation may help guide surgical planning. Currently there is no standardized preoperative EDX protocol. This study reviews the EDX workup preceding PNT surgery in cervical SCI and proposes an informed EDX protocol to assist with surgical planning. The PICO (Population, Intervention, Comparison, Outcome) framework was used to formulate relevant Medical Subject Headings (MeSH) terms and identify published cases of PNT in cervical SCI in Medline, Embase, CINAHL, and Emcare databases in the last 10 years. The EDX techniques evaluating putative donor nerves, recipient nerve branches, time sensitivity of nerve transfer and other electrophysiological parameters were summarized to guide creation of a preoperative EDX protocol. Needle electromyography (EMG) was the most commonly used EDX technique to identify healthy donor nerves. Although needle EMG has also been used on recipient nerves, compound muscle action potential amplitudes may provide a more accurate determination of recipient nerve health and time sensitivity for nerve transfer. Although there has been progress in presurgical EDX evaluation, EMG and nerve conduction study approaches are variable, and each has limitations in their utility for preoperative planning. There is need for standardization in the EDX evaluation preceding PNT surgery to assist with donor and recipient nerve selection, surgical timing and to optimize outcomes. Based on results of this review, herein we propose the PreSCIse (PRotocol for Electrodiagnosis in SCI Surgery of the upper Extremity) preoperative EDX panel to achieve said goals through an interdisciplinary and patient‐centered approach.
Advancing health equity in pediatric cancer through implementation of universal family psychosocial risk screening
Authors: Deatrick Janet A. , Kazak Anne E. , Scialla Michele A. , Madden Rebecca E. , McDonnell Glynnis A. , Okonak Katherine , Barakat Lamia P. 
Published: June 2022

AbstractBackgroundUnaddressed psychosocial risks may contribute to disparities in cancer care outcomes and may be addressed by early psychosocial risk screening. In a study implementing universal family psychosocial risk screening in 18 children's cancer programs in the United States, parents, clinicians, and organizational leaders described the importance of universal screening to health equity.PurposesThe purposes of this study were to (1) describe the perspectives of parents, clinicians, and organizational leaders regarding the importance of universal family psychosocial risk screening in childhood cancer care and (2) identify barriers and facilitators to improving health equity and decreasing health disparities in childhood cancer through universal family psychosocial screening.MethodsNineteen participants (parent advocates, clinicians, leaders in professional organizations and healthcare policy) were interviewed. Directed content analysis was used to identify thematic descriptions.ResultsTheme 1: Personal (individual child and family) and systemic barriers to health care contribute to health disparities and can be identified by universal family psychosocial risk screening in pediatric cancer. Theme 2: Universal family psychosocial risk screening in pediatric cancer creates the opportunity for health equity through personalized psychosocial care. Theme 3: Recognition of health inequities and guidance from the Standards of Psychosocial Care for Children with Cancer and their Families suggest that clinicians and healthcare systems are ethically obligated to screen, provide resources, and advocate for services to meet identified needs.ConclusionsUniversal family psychosocial risk screening in pediatric oncology creates the opportunity to support efforts for health equity by guiding delivery of personalized psychosocial care.Trial registrationNCT04446728 23 June 2020.
Cancer‐related cognitive impairment in survivors of adolescent and young adult non‐central nervous system cancer: A scoping review
Authors: Vizer Lisa M. , Mikles Sean P. , Piepmeier Aaron T. 
Published: June 2022

AbstractObjectivesCancer‐related cognitive impairments (CRCI) are common after treatment and can have important impacts on the lives of adolescent and young adult (AYA) cancer survivors—those cancer survivors diagnosed between ages 15 and 39. However, most research focuses on survivors diagnosed under age 15 or over age 39 so we know relatively little about CRCI among AYA survivors of non‐central nervous system (CNS) cancers. Here we review the research on CRCI among AYA survivors of non‐CNS cancers to determine prevalence, associated factors, and impact on survivors' lives as well as implications for future research.MethodsIn November 2021 we performed a systematic search of the literature in MEDLINE, Web of Science, PsycInfo, CINAHL, EMBASE, and Cochrane Central Register of Controlled Trials to identify peer‐reviewed English language articles describing original research with at least one cognitive outcome and conducted with AYA survivors of non‐CNS cancer diagnosed as AYAs. We screened 6003 articles and 21 met eligibility criteria. Guided by the PRISMA‐ScR Checklist, we extracted study information to meet review objectives.ResultsMost studies employed cross‐sectional surveys or interviews, though some employed longitudinal methods, neurocognitive assessments, or brain imaging. From the subset of articles that reported a prevalence we calculated a weighted mean prevalence of 25.75% and weighted median prevalence of 27.8%. The factors associated with CRCI included female gender, higher dose chemotherapy, and comorbidities. CRCI impacted the lives of AYA survivors through impaired role functioning, financial toxicity, and unmet needs.ConclusionsCRCI is highly prevalent among non‐CNS cancer survivors diagnosed as AYAs and impacts quality of life and role functioning. This review suggests a need for further longitudinal, imaging, and mixed methods research and provision of resources to help achieve better quality of life and educational and occupational attainment during what is potentially a decades‐long survivorship period. However, although interventions might improve cognition and functioning, the review identified only one pilot study. Digital interventions may be a practical and effective option for this age group, but they have yet to be adequately investigated.
Immediate and long‐term effects of manual chest compression and decompression maneuver on patients receiving invasive mechanical ventilation
Authors: Biarzi Karla Francieli , Severo Sabrina Brandalise , Baptistella Antuani Rafael 
Published: June 2022

AbstractBackgroundIt has been reported that the manual chest compression and decompression (MCCD) maneuver can increase lung volume in patients receiving invasive mechanical ventilation (IMV), but some important questions related to this maneuver require answers: how long the effects of MCCD on lung volume remain, and whether there are effects on other respiratory and hemodynamic variables.MethodsPatients receiving IMV support in an intensive care unit (ICU) with signs of hypoventilation, hypoexpansion, or atelectasis were eligible to receive the MCCD maneuver. Immediately before the maneuver, respiratory and hemodynamic parameters were collected. Then, 20 MCCD maneuvers were performed while measured the same parameters. After 10 min, all parameters were measured again. The primary outcome was the tidal volume (Vt) during the MCCD maneuver and after 10 min compared to the previous Vt.ResultsOf the 255 patients who were mechanically ventilated in the study period, 105 patients composed the final cohort. The MCCD increased inspiratory tidal volume (iVt), expiratory tidal volume (eVt), and chest dynamic compliance (Cdyn) during the application of the maneuver, but after 10 min, these parameters returned to their basal levels. The MCCD maneuver did not change the peak pressure, respiratory rate, peripheral oxygen saturation (SpO2), heart rate, or blood pressure. There was no difference in increased iVt in patients with sedation, respiratory comorbidity, or obesity. Further, there was no association between the iVt response to the MCCD and the admission diagnosis, and no correlation with the ICU length of stay, IMV duration, or APACHE II score.Implications of Physiotherapy PracticeWe concluded that MCCD increased iVt, eVt, and Cdyn during the application of the maneuver, but this effect was not observed after 10 min. Randomized controlled trials should be performed in the future to investigate the mechanism involved in increasing Vt and the possible impact of the MCCD maneuver on ICU outcomes.