bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease control and psychiatric comorbidity among adolescents with chronic medical conditions: a single-centre retrospective study
Authors: Kallio Mira , Tornivuori Anna , Miettinen Päivi , Kolho Kaija-Leena , Culnane Evelyn , Sawyer Susan , Kosola Silja 
Published: February 2023

BackgroundTo investigate disease control, psychiatric comorbidity, substance use and their possible associations in adolescents with chronic medical conditions before transfer to adult healthcare.MethodsWe collected clinical data from the year preceding transfer of care and psychiatric data from the records of the paediatric hospital in Helsinki, Finland (population base 1.7 million). Participants were grouped into three disease and/or adherence control categories (good, some evidence of concern, poor) based on clinical data from the medical records of the year preceding the transfer of care. Participants completed the Adolescent’s Substance Use Measurement Questionnaire before transfer of care and were divided into four risk subgroups accordingly.ResultsIn total, 253 adolescents (mean age 17.3 years, SD 1.2) from six paediatric subspecialties participated in this study. Disease control and/or adherence were rated as good in 28% (n=70), moderate in 42% (n=105) and poor in 30% (n=76) in the year before participants transferred to adult health services. A quarter of participants had at least one psychiatric diagnosis during adolescence. Adolescents with concomitant psychiatric diagnoses more often had poor disease control of their chronic medical condition than adolescents with only a medical condition (44% vs 26%; n=25 of 59 vs 51 of 194, respectively). More than half of adolescents (56%) were abstinent or used substances infrequently; 10% (n=26) reported hazardous substance use.ConclusionsPsychiatric comorbidity in adolescents with chronic medical conditions is common. Its negative association with disease control and possible substance use should be considered in the transition process to adult health services.
One-person versus two-person mask ventilation in preterm infants at birth: a pilot randomised controlled trial
Authors: Shah Dharmesh , Tracy Mark B , Hinder Murray Kenneth , Badawi Nadia 
Published: February 2023

BackgroundMask leak and airway obstruction are common with mask ventilation in newborn infants, leading to suboptimal ventilation. We aimed to perform a pilot study measuring respiratory mechanics during one-person and two-person mask ventilation in preterm infants at birth.MethodsInfants less than 30 weeks’ gestation were eligible for the study. In the two-person method, one person holds the mask in place and the other provides positive pressure ventilation compared with the standard one-person mask hold. A respiratory function monitor was used in line with a T-piece resuscitator to measure mask leak and airway obstruction. Deferred consent was obtained.ResultsTwenty-five infants were recruited. The mean (SD) birth weight was 920.4 g (188.3), and mean (SD) gestational age was 27.3 weeks (3.0). Percentage mask leak was higher in the one-person mask method (26.4±18.5) compared with the two-person mask method (17.6±9.3) (p=0.018). The mean (SD) expired tidal volume (VTe, mL) in breaths with leak was 3.9 (1.57) in the one-person method compared with 3.05 (1.0) the two-person method (p=0.31). A significantly lower mean (SD) end-tidal carbon dioxide (EtCO2,mm Hg) was measured at 25.3 (9.9) in breaths with mask leak, compared with 30.8 (12.1) in breaths without leak. The breaths with airway obstruction had lower mean EtCO2(25.9 vs 30.8, p=0.003) and lower mean VTe(1.71 vs 6.95, p<0.001).ConclusionMask leak and airway obstruction are common in resuscitation of preterm infants at birth. The use of the two-person mask technique is effective and it could be a useful option if mask ventilation with the one-person method is not effective.Trial registration numberACTRN12614000245695.
Tuned activation of MSLN-CAR T cells induces superior antitumor responses in ovarian cancer models
Authors: Schoutrop Esther , Poiret Thomas , El-Serafi Ibrahim , Zhao Ying , He Rui , Moter Alina , Henriksson Johan , Hassan Moustapha , Magalhaes Isabelle , Mattsson Jonas 
Published: February 2023

BackgroundLimited persistence of functional CAR T cells in the immunosuppressive solid tumor microenvironment remains a major hurdle in the successful translation of CAR T cell therapy to treat solid tumors. Fine-tuning of CAR T cell activation by mutating CD3ζ chain immunoreceptor tyrosine-based activation motifs (ITAMs) in CD19-CAR T cells (containing the CD28 costimulatory domain) has proven to extend functional CAR T cell persistence in preclinical models of B cell malignancies.MethodsIn this study, two conventional second-generation MSLN-CAR T cell constructs encoding for either a CD28 co-stimulatory (M28z) or 4-1BB costimulatory (MBBz) domain and a novel mesothelin (MSLN)-directed CAR T cell construct encoding for the CD28 costimulatory domain and CD3ζ chain containing a single ITAM (M1xx) were evaluated using in vitro and in vivo preclinical models of ovarian cancer. Two ovarian cancer cell lines and two orthotopic models of ovarian cancer in NSG mice were used: SKOV-3 cells inoculated through microsurgery in the ovary and to mimic a disseminated model of advanced ovarian cancer, OVCAR-4 cells injected intraperitoneally. MSLN-CAR T cell treatment efficacy was evaluated by survival analysis and the characterization and quantification of the different MSLN-CAR T cells were performed by flow cytometry, quantitative PCR and gene expression analysis.ResultsM1xx CAR T cells elicited superior antitumor potency and persistence, as compared with the conventional second generation M28z and MBBz CAR T cells. Ex vivo M28z and MBBz CAR T cells displayed a more exhausted phenotype than M1xx CAR T cells as determined by co-expression of PD-1, LAG-3 and TIM-3. Furthermore, M1xx CAR T cells showed superior ex vivo IFNy, TNF and GzB production and were characterized by a self-renewal gene signature.ConclusionsAltogether, our study demonstrates the enhanced therapeutic potential of MSLN-CAR T cells expressing a mutated CD3ζ chain containing a single ITAM for the treatment of ovarian cancer. CAR T cells armored with calibrated activation potential may improve the clinical responses in solid tumors.
Roles of light transmission aggregometry and CYP2C19 genotype in predicting ischaemic complications during interventional therapy for intracranial aneurysms
Authors: Zhou Yangyang , Li Wenqiang , Wang Chao , Xie Ruhang , Zhu Yongnan , Peng Qichen , Zhang Limin , Zhang Hongqi , Gu Yuxiang , Mu Shiqing , Liu Jian , Yang Xinjian 
Published: February 2023

Background and purposeLight transmission aggregometry (LTA) and CYP2C19 genotype analysis are commonly used to evaluate the antiplatelet effects of clopidogrel during the interventional treatment of intracranial aneurysms. The aim of this study was to determine which test can predict ischaemic events during these treatments.MethodsPatient demographic information, imaging data, laboratory data and ischaemic complications were recorded. LTA and CYP2C19 genotype results were compared, and multiple linear regression was performed to examine factors related to platelet reactivity. Multivariate regression analysis was performed to determine whether LTA and CYP2C19 could predict ischaemic complications and to identify other clinical risk factors. Receiver operating characteristic curve analysis was conducted to calculate the cut-off value for predicting ischaemic complications. A subgroup analysis was also performed for different CYP2C19 genotype metabolisers, as well as for patients with flow diverters and traditional stents.ResultsA total of 379 patients were included, of which 22 developed ischaemic events. Maximum platelet aggregation induced by ADP (ADP-MPA) could predict ischaemic events (p<0.001; area under the curve, 0.752 (95% CI 0.663 to 0.842)), and its cut-off value was 41.5%. ADP-MPA (p=0.001) and hypertension duration >10 years (p=0.022) were independent risk factors for ischaemic events, while the CYP2C19 genotype was not associated with ischaemic events. In the subgroup analysis, ADP-MPA could predict ischaemic events in fast metabolisers (p=0.004) and intermediate metabolisers (p=0.003). The cut-off value for ischaemic events was lower in patients with flow diverters (ADP-MPA=36.4%) than in patients with traditional stents (ADP-MPA=42.9%).ConclusionsADP-MPA can predict ischaemic complications during endovascular treatment of intracranial aneurysms. Patients with flow diverters require stronger antiplatelet medication than patients with traditional stents.
Cervical spine flexion-extension radiography versus magnetic resonance imaging in pediatric patients following blunt traumatic injury
Authors: Zhang Jeff F , Umenta Janet , Ali Adil , Reynolds Renee , Ham Phillip Benson , Thomas Richard D , Piryani Ravi , Izhar Muhammad , Wrotniak Brian , Swayampakula Anil K 
Published: February 2023

BackgroundIn pediatric trauma patients, 60–80% of spinal cord injuries involve the cervical vertebrae. While the American College of Radiology offers guidelines for best imaging practices in the setting of acute pediatric trauma, there is a lack of uniformity in imaging-decision protocols across institutions. MRI has been shown to demonstrate high sensitivity for both bony and ligamentous injuries while also avoiding unnecessary radiation exposure in the pediatric patient population. However, the efficacy of flexion-extension (FE) radiography following initial MRI has not been evaluated in children. Our hypothesis is that FE radiography conducted following an initial MRI does not contribute significant diagnostic information or reduce time to cervical collar removal and thus can be removed from institutional protocols in order to avoid unnecessary testing and reduce pediatric radiation exposure.MethodsTrauma data were collected for pediatric patients presenting with suspected acute cervical spine injury from 2014 to 2021. A total of 108 patients were subdivided into 41 patients who received “MRI Only” and 67 patients who received both “MRI and FE” diagnostic cervical spine imaging. Chi-square testing and t-tests were performed to determine differences between MRI and FE radiographic detection rates of bony and ligamentous injuries in the subgroups.ResultsIn patients for whom FE did not find any injury, MRI detected bony and ligamentous injuries in 9/63 and 12/65 cases, respectively. In 3/21 (14.3%) cases in which MRI detected a bony and/or ligamentous injury and FE did not, patients eventually required surgical intervention for c-spine stabilization. No patients required surgical fixation when FE radiography showed an abnormality and MRI was normal. Addition of follow-up FE radiography after initial MRI did not have a significant effect on overall hospital length of stay (MRI Only vs MRI+FE: 9.2±12.0 days vs 8.6±13.5 days, p=0.816) or on rates of collar removal at discharge or greater than 48 hours after imaging (MRI Only vs MRI+FE: 41.5% vs 56.7%, p=0.124).ConclusionsFE radiography following initial MRI did not have a significant effect on reducing time to cervical collar removal or overall hospital length of stay. In addition, in 3 of 6 cases (50.0%) in which surgical fixation was required, MRI detected ligamentous and/or bony injury while FE radiography was normal.Level of EvidenceThis study contributes Level 2b scientific evidence consistent with a well-designed cohort or case-control analytic study.
2022 Alonzo Church Award Announcement
Authors: Kozen Dexter 
Published: February 2023

The ACM Special Interest Group on Logic (SIGLOG), the European Association for Theoretical Computer Science (EATCS), the European Association for Computer Science Logic (EACSL), and the Kurt Goedel Society (KGS) are pleased to announce that
has been selected as the winner of the
2022 Alonzo Church Award for Outstanding Contributions to Logic and Computation
for his fundamental work on developing the theory and applications of Kleene Algebra with Tests, an equational system for reasoning about iterative programs, published in:
Kleene Algebra with Tests. ACM Transactions on Programming Languages and Systems 19(3): 427-443 (1997).
Germline Cancer Gene Expression Quantitative Trait Loci Are Associated with Local and Global Tumor Mutations
Authors: Liu Yuxi , Gusev Alexander , Kraft Peter 
Published: February 2023

AbstractSomatic mutations drive cancer development and are relevant to patient responses to treatment. Emerging evidence shows that variations in the somatic genome can be influenced by the germline genetic background. However, the mechanisms underlying these germline–somatic associations remain largely obscure. We hypothesized that germline variants can influence somatic mutations in a nearby cancer gene (“local impact”) or a set of recurrently mutated cancer genes across the genome (“global impact”) through their regulatory effect on gene expression. To test this hypothesis, tumor targeted sequencing data from 12,413 patients across 11 cancer types in the Dana-Farber Profile cohort were integrated with germline cancer gene expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression Project. Variants that upregulate ATM expression were associated with a decreased risk of somatic ATM mutations across 8 cancer types. GLI2, WRN, and CBFB eQTL were associated with global tumor mutational burden of cancer genes in ovarian cancer, glioma, and esophagogastric carcinoma, respectively. An EPHA5 eQTL was associated with mutations in cancer genes specific to colorectal cancer, and eQTL related to expression of APC, WRN, GLI1, FANCA, and TP53 were associated with mutations in genes specific to endometrial cancer. These findings provide evidence that germline–somatic associations are mediated through expression of specific cancer genes, opening new avenues for research on the underlying biological processes.Significance:Analysis of associations between the germline genetic background and somatic mutations in patients with cancer suggests that germline variants can influence local and global tumor mutations by altering expression of cancer-related genes.See related commentary by Kar, p. 1165.
HPV-based Cervical Cancer Screening on Self-samples in the Netherlands: Challenges to Reach Women and Test Performance Questions
Authors: Arbyn Marc , Costa Stefanie , Latsuzbaia Ardashel , Kellen Eliane , Girogi Rossi Paolo , Cocuzza Clementina E. , Basu Partha , Castle Philip E. 
Published: February 2023

Abstract
In 2017, cervical cancer screening in the Netherlands switched from cytology to human papillomavirus (HPV) testing using the validated PCR-based cobas 4800. Women could order and subsequently received a free self-sampling kit (Evalyn Brush) at their home address instead of clinician sampling. In the laboratory, the shipped brush was placed into 20 mL of PreservCyt fluid, before testing. In the first 2 years of the new program, only 7% of screening tests were performed on a self-sample. Those who chose self-sampling versus clinician sampling were more likely to have never been screened previously and differed also with respect to sociodemographic factors. Subsequent more active promotion and increasing the ease to obtain kits increased the proportion opting for self-sampling (16% in 2020). HPV positivity and detection rate of precancer (CIN3+) were lower in the self-sampling compared with the clinician-sampling group (adjusted ORs of 0.65 and 0.86, respectively). Although population differences may partially explain these results, self-samples may have been too dilute, thereby reducing the analytic and clinical sensitivity. The Dutch findings demonstrate the importance of optimizing outreach, specimen handling and testing protocols for self-samples to effectively screen the target population and reach in particular the women at highest risk for cervical cancer.
See related article by Aitken et al., p. 183
Racial Differences in Breast Cancer Therapeutic Toxicity: Implications for Practice
Authors: Rosenzweig Margaret Quinn , Mazanec Susan R. 
Published: February 2023

Abstract
Disparities in treatment intensity can contribute to racial disparities in overall breast cancer survival. A natural extension of measuring racial disparities in treatment intensity is consideration of the distribution of treatment toxicities, symptoms, and distress that lead to chemotherapy dose reductions, holds or early termination. There is growing evidence that therapeutic toxicity during early-stage breast cancer treatment may be greater among Black women than White. Important components of symptom management involve the communication of symptoms, the self-care abilities of the patient, the patient's perception of the clinical encounter, and the patient centeredness of the clinical encounter. Racial differences in the symptom reporting, the clinical “reception” and response to symptoms, the prescribed management, and the patient adherence to symptom management requires further investigation. Further research must also consider the structural inequities, as well as institutional and interpersonal racism that contribute to racial differences in cancer symptom burden leading to potential decreases in dose intensity of potentially life-saving early cancer treatment.
See related article by Hu et al., p. 167
Elucidating the Drivers for the Rising Incidence of Early-Onset Colorectal Cancer: How Ecologic Studies Could Help and What Is Next
Authors: Ni Peiyun , Lansdorp-Vogelaar Iris , Zauber Ann G. , Cao Yin 
Published: February 2023

Abstract
The incidence of colorectal cancer diagnosed before age 50, often referred to as early-onset colorectal cancer, has been increasing, whereas the overall colorectal cancer incidence has declined. Elucidating the drivers for the rising burden of early-onset colorectal cancer is a priority in cancer epidemiology and prevention. In this issue of Cancer Epidemiology, Biomarkers & Prevention, Chen and colleagues demonstrated that ecologic studies are a helpful method to reveal emerging risk factors at the population level and concluded that alcohol use might be a potential contributor to the rising incidence of early-onset colorectal cancer. Moving forward, because of the observed birth cohort effect in early-onset colorectal cancer, where younger generations have a steeper increase, hypothesis-driven investigations on emerging risk factors in recent generations, especially during early life, are warranted. Ultimately, the identified risk factors could be integrated with well-established microsimulation models of colorectal cancer, powerful tools that can simultaneously capture population-level secular changes in risk factors, relative risk estimates for each risk factor, and the natural history of colorectal cancer. This would allow us to quantitatively estimate the explained and unexplained portion of the rising incidence of early-onset colorectal cancer by calendar period and birth cohorts, and to help identify priorities in etiologic research, prevention, and early detection.
See related article by Chen et al., p. 217
Discovery of Targets for Immune–Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha
Authors: Sahu Avinash , Wang Xiaoman , Munson Phillip , Klomp Jan P.G. , Wang Xiaoqing , Gu Shengqing Stan , Han Ya , Qian Gege , Nicol Phillip , Zeng Zexian , Wang Chenfei , Tokheim Collin , Zhang Wubing , Fu Jingxin , Wang Jin , Nair Nishanth Ulhas , Rens Joost A.P. , Bourajjaj Meriem , Jansen Bas , Leenders Inge , Lemmers Jaap , Musters Mark , van Zanten Sanne , van Zelst Laura , Worthington Jenny , Liu Jun S. , Juric Dejan , Meyer Clifford A. , Oubrie Arthur , Liu X. Shirley , Fisher David E. , Flaherty Keith T. 
Published: February 2023

AbstractDrugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell–specific regulators that simultaneously modulate tumor immunity and another oncogenic pathway and then used it to identify 38 candidate immune–metabolic regulators. We show the tumor activities of these regulators stratify patients with melanoma by their response to anti–PD-1 using machine learning and deep neural approaches, which improve the predictive power of current biomarkers. The topmost identified regulator, ESRRA, is activated in immunotherapy-resistant tumors. Its inhibition killed tumors by suppressing energy metabolism and activating two immune mechanisms: (i) cytokine induction, causing proinflammatory macrophage polarization, and (ii) antigen-presentation stimulation, recruiting CD8+ T cells into tumors. We also demonstrate a wide utility of BipotentR by applying it to angiogenesis and growth suppressor evasion pathways. BipotentR (http://bipotentr.dfci.harvard.edu/) provides a resource for evaluating patient response and discovering drug targets that act simultaneously through multiple mechanisms.Significance:BipotentR presents resources for evaluating patient response and identifying targets for drugs that can kill tumors through multiple mechanisms concurrently. Inhibition of the topmost candidate target killed tumors by suppressing energy metabolism and effects on two immune mechanisms.This article is highlighted in the In This Issue feature, p. 517
Black in Cancer: Two Years of Empowering the Next Generation
Authors: Bourne Christopher M. , Henderson Henry J. , White Elshaddai , Morris Julia , Bah Mamadou A. , Harewood Rhea , Pierre Stephanie , Martins Tanimola , Ntereke Tumisang , White Briana , Bonner Sigourney 
Published: February 2023

Summary:
In the 2 years since the inception of Black in Cancer, we have modeled an action-oriented commitment to improving Black representation across all levels of the cancer spectrum. We reflect on our successes and consider new ways to innovate and inspire the cancer community.
O papel das agências reguladoras na tutela dos direitos do consumidor
Authors: Maradei Júnior João Carlos 
Published: February 2023

Na década de 1990, o Estado brasileiro transferiu atividades econômicas, até então sob a égide do setor público, para a iniciativa privada. Nesse contexto, surgem as agências reguladoras no Brasil. Nesse artigo, iniciamos com um breve histórico sobre a criação das agências reguladoras, com destaque para o modelo americano. Seguimos com abordagem acerca dos motivos que levaram a sua estruturação no Brasil para, então, analisar nuances da Lei Geral das Agências Reguladoras em âmbito federal, sempre sob a perspectiva da tutela dos direitos consumeristas. Trazemos exemplos, como do setor de energia elétrica, para demonstrar que, mesmo em período pandêmico, a “manutenção do equilíbrio” das relações de consumo, quando o assunto é tarifário, pende para um único lado. Abordamos sobre o recente regramento do setor de saneamento, refletindo sobre a necessidade de expansão dos serviços, porém, sem que isso onere mais o consumidor. Enfim, procuramos analisar criteriosamente se a atividade regulatória do Estado tem espelhado os anseios da coletividade ou tem privilegiado setores econômicos e políticos. Ponderamos, por fim, ser fundamental a harmonização dos interesses e a observância dos ditames constitucionais acerca dos direitos dos consumidores para que o modelo regulatório brasileiro atenda os fins para os quais se destina.