bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small cell lung cancer transformation and tumor heterogeneity after sequential targeted therapy and immunotherapy in EGFR-mutant non-small cell lung cancer: A case report
Authors: Yang Meng-Hang , Yu Jia , Cai Chen-Lei , Li Wei 
Published: December 2022

BackgroundHistological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of mechanisms of the acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). However, SCLC transformation and tumor heterogeneity have never been reported in sequential targeted therapy and immunotherapy.Case presentationHere, we described a patient with advanced EGFR-mutant NSCLC, who received erlotinib and underwent the resistance with EGFR T790M (–). The patient then received chemotherapy plus immunotherapy of programmed cell death 1 (PD-1) inhibitor, encountered progression with pathological transformation from NSCLC to SCLC that was overcome by chemotherapy of etoposide plus carboplatin (EC) with the main lesion significantly shrinking while metastatic nodules increasing. The pathology of the metastatic nodule showed NSCLC with EGFR T790M (+). Based on the tumor heterogeneity, EC chemotherapy combined with osimertinib was used, and patients responded well. The patient experienced four lung biopsies in all, which helped to provide the patient with precise treatment.ConclusionsThis case suggested that SCLC transformation and tumor heterogeneity should be paid attention to when disease progression occurred in advanced NSCLC whether receiving targeted therapy or immunotherapy.
Turbulence of glutamine metabolism in pan-cancer prognosis and immune microenvironment
Authors: He Songjiang , Zhang Shi , Yao Yi , Xu Bin , Niu Zhili , Liao Fuben , Wu Jie , Song Qibin , Li Minglun , Liu Zheming 
Published: December 2022

IntroductionGlutamine is characterized as the nutrient required in tumor cells. The study based on glutamine metabolism aimed to develop a new predictive factor for pan-cancer prognostic and therapeutic analyses and to explore the mechanisms underlying the development of cancer.MethodsThe RNA-sequence data retrieved from TCGA, ICGC, GEO, and CGGA databases were applied to train and further validate our signature. Single-cell RNA transcriptome data from GEO were used to investigate the correlation between glutamine metabolism and cell cycle progression. A series of bioinformatics and machine learning approaches were applied to accomplish the statistical analyses in this study.ResultsAs an individual risk factor, our signature could predict the overall survival (OS) and immunotherapy responses of patients in the pan-cancer analysis. The nomogram model combined several clinicopathological features, provided the GMscore, a readable measurement to clinically predict the probability of OS and improve the predictive capacity of GMscore. While analyzing the correlations between glutamine metabolism and malignant features of the tumor, we observed that the accumulation of TP53 inactivation might underlie glutamine metabolism with cell cycle progression in cancer. Supposedly, CAD and its upstream genes in glutamine metabolism would be potential targets in the therapy of patients with IDH-mutated glioma. Immune infiltration and sensitivity to anti-cancer drugs have been confirmed in the high-risk group.DiscussionIn summary, glutamine metabolism is significant to the clinical outcomes of patients with pan-cancer and is tightly associated with several hallmarks of a malignant tumor.
Deterioration in glycemic control on schooldays among children and adolescents with type 1 diabetes: A continuous glucose monitoring-based study
Authors: Ding Yu , Zhang Wenhao , Wu Xiumei , Wei Tian , Wang Xulin , Zheng Xueying , Luo Sihui 
Published: December 2022

BackgroundTo investigate the effect of school life by comparing the glycemic control between holidays and schooldays in children and adolescents with type 1 diabetes (T1D).MethodsThis observational study enrolled school-aged students with T1D (aged 6–19) from September 2019 to July 2021. Continuous glucose monitoring (CGM) records were processed and divided into holidays and schooldays. Other information was collected via questionnaires. We compared the results using paired T-test, Wilcoxon paired test and logistic regression analysis.Results78 paticipants were included (40 boys, mean age 9.95 years). A total of 142,945 h of CGM data were analyzed. Overall, TIR (3.9–7.8 mmol/L) during holidays was better than schooldays [56.97 (SD 15.03) vs. 55.87 (15.06), %, p = 0.039]. On nocturnal (0–6 am) glycemic fluctuation, TIR was longer in children aged 6–10 [60.54 (17.40) vs. 56.98 (SD 16.32), %, p = 0.012] during holiday and TAR (7.8 mmol/L) was shorter [31.54 (17.54) vs. 35.54 (16.95), %, p = 0.013], compared with schooldays. In adolescents aged 10–19 years, TAR was also significantly shorter during holidays. Stratified analysis showed that girls, patients with longer duration, and insulin pump users had more pronounced worsening of nighttime glycemia on schooldays. Logistic regression analysis showed that girls had higher risk of worse nocturnal glycemic control [3.26, 95% CI: (1.17, 9.72), p = 0.027] and nocturnal hyperglycemia [OR = 2.95, 95% CI: (1.08, 8.56), p = 0.039], compared to boys.ConclusionsChildren and adolescents with T1D were found to have worse glycemic control in nighttime during schooldays.
Five vs. two initial rescue breaths during infant basic life support: A manikin study using bag-mask-ventilation
Authors: Geerts Anke , Herbelet Sandrine , Borremans Gautier , Coppens Marc , Christiaens-Leysen Erik , Van de Voorde Patrick 
Published: December 2022

Background and objectivesChildren are more likely to suffer a hypoxic-ischaemic cause for cardiac arrest. Early ventilation may provide an advantage in outcome during paediatric cardiopulmonary resuscitation [CPR]. European Resuscitation Council guidelines recommend five initial rescue breaths [IRB] in infants, stemming from the hypothesis that rescuers might need 5 attempts in order to deliver 2 effective ventilations. This study aimed to verify this hypothesis.MethodsParticipants (n = 112, convenience sample) were medical students from the Faculty of Medicine and Health Sciences Ghent University, Belgium. Students were divided into duos and received a 15 min just-in-time training regarding the full CPR-cycle using BMV. Participants then performed five cycles of 2-person CPR. The IRB were given by 1-person BMV, as opposed to a 2-persons technique during the further CPR-cycle. Correct ventilations for the infant were defined as tidal volumes measured (Laerdal® Q-CPR) between 20 and 60 ml, with n = 94 participants included in the analysis. The primary outcome consisted of the difference in the % of medical student duos providing at least 2 effective IRB between 2 and 5 attempts.ResultsOff all duos, 55,3% provided correct volumes during their first 2 initial ventilations. An increase up to 72,4% was noticed when allowing 5 ventilations. The proportional difference between 2 and 5 IRB allowed was thus significant [17,0%, 95% confidence interval (5.4; 28.0)].ConclusionIn this manikin study, 5 IRB attempts during infant CPR with BMV increased the success rate in delivering 2 effective ventilations. Besides, students received training emphasizing the need for 5 initial rescue breaths. This study provides evidence supporting European Resuscitation Council guidelines.
Beta-blockers in post-acute myocardial infarction patients: Drug prescription patterns from 2018 to Italy’s first wave of the COVID-19 pandemic
Authors: Olmastroni Elena , Galimberti Federica , Catapano Alberico L. , Tragni Elena , Casula Manuela 
Published: December 2022

Background: Major guidelines recommend the initiation of a beta-blocker therapy after an acute myocardial infarction (AMI). We aimed to map the treatment pathway of beta-blockers for AMI survivors during the first wave of COVID-19 pandemic in Italy and to investigate predictors for treatment non-initiation.Methods: Healthcare utilization databases of Lombardy Region were investigated. Subjects aged ≥18 years who were hospitalised with AMI in the period February-March-April of 2018, 2019, and 2020 were included, and followed for 30 days from the discharge date, to investigate whether they presented a first prescription of beta-blockers. A multivariate logistic model was performed to evaluate the effect of several covariates on the probability of not receiving a post-AMI beta-blocker therapy.Results: The cohorts comprised 2259, 2383, and 1932 individuals who were hospitalised with AMI in the 3-month period in 2018, 2019, and 2020, respectively. Overall in 2020, about 58–60% of individuals with AMI received a prescription of beta-blockers within 1 month after the discharge. A continuous decreasing trend over time was observed. Men were 30% more likely to start the treatment than women, increasing age was associated with significant increasing probability of not receiving a post-infarction beta-blocker therapy, while having received an antihypertensive or lipid-lowering treatment, or having been hospitalized for heart failure prior to the AMI hospitalization reduced the likelihood of not being treated with beta-blockers.Conclusion: The initiation of beta-blocker treatment after AMI remains an under-prescribed practice, that does not seem to have been further affected by the first wave of the COVID-19 pandemic.
Is the vesicular nucleotide transporter a molecular target of eicosapentaenoic acid?
Authors: Moriyama Yoshinori , Hasuzawa Nao , Nomura Masatoshi 
Published: December 2022

Vesicular nucleotide transporter (VNUT), an active transporter for nucleotides in secretory vesicles, is responsible for the vesicular storage of ATP and plays an essential role in purinergic chemical transmission. Inhibition of VNUT decreases the concentration of ATP in the luminal space of secretory vesicles, followed by decreased vesicular ATP release, resulting in the blockade of purinergic chemical transmission. Very recently, Miyaji and colleagues reported that eicosapentaenoic acid (EPA) is a potent VNUT inhibitor and effective in treating neuropathic and inflammatory pain and insulin resistance through inhibition of vesicular storage and release of ATP. However, our validation study indicated that, in bovine adrenal chromaffin granule membrane vesicles, EPA inhibited the formation of an electrochemical gradient of protons across the membrane with the concentration of 50% inhibition (IC50) being 1.0 μM without affecting concanamycin B-sensitive ATPase activity. Essentially, similar results were obtained with proteoliposomes containing purified vacuolar H+-ATPase. Consistent with these observations, EPA inhibited the ATP-dependent uptakes of ATP and dopamine by chromaffin granule membrane vesicles, with ID50 being 1.2 and 1.0 μM, respectively. Furthermore, EPA inhibited ATP-dependent uptake of L-glutamate by mouse brain synaptic vesicles with ID50 being 0.35 μM. These results indicate that EPA at sub-μM acts as a proton conductor and increases proton permeability across the membrane, regardless of the presence or absence of VNUT, thereby inhibiting non-specifically the vesicular storage of neurotransmitters. Thus, EPA may affect a broader range of chemical transmission than proposed.
Development and validation of a new non-disease-specific survey tool to assess self-reported adherence to medication
Authors: Larsen Rønnaug Eline , Pripp Are Hugo , Krogstad Tonje , Johannessen Landmark Cecilie , Holm Lene Berge 
Published: December 2022

Background: Patients’ non-adherence to medication affects both patients themselves and healthcare systems. Consequences include higher mortality, worsening of disease, patient injuries, and increased healthcare costs. Many existing survey tools for assessing adherence are linked to specific diseases and assessing medication-taking behavior or identifying barriers or beliefs. This study aimed to develop and validate a new non-disease-specific survey tool to assess self-reported medication-taking behavior, barriers, and beliefs in order to quantify the causes of non-adherence and measure adherence.Methods: The survey tool was developed after literature searches and pilot testing. Validation was conducted by assessing the psychometric properties of content, construct, reliability, and feasibility. Content validity was assessed by subject matter experts and construct validity by performing exploratory factor analysis. Reliability assessment was performed by calculating internal consistency, Cronbach’s alpha and test/retest reliability, intraclass correlation coefficient (ICC), and standard error of measurement (SEm). A receiver operating characteristic (ROC) curve and the Lui method were used to calculate the statistical cut-off score for good versus poor adherence. Survey responses from Norwegian medication users over 18 years recruited via social media were used for the factor analysis and Cronbach’s alpha.Results: The final survey tool contains 37 causes of non-adherence connected to medication-taking behavior and barriers to adherence and beliefs associated with adherence. The overall result for all 37 items demonstrated reliable internal consistency, Cronbach’s alpha = 0.91. The factor analysis identified ten latent variables for 29 items, explaining 61.7% of the variance. Seven of the latent variables showed reliable internal consistency: medication fear and lack of effect, conditional practical issues, pregnancy/breastfeeding, information issues, needlessness, lifestyle, and avoiding stigmatization (Cronbach’s alpha = 0.72–0.86). Shortage showed low internal consistency (Cronbach’s alpha = 0.59). Impact issues and personal practical issues showed poor internal consistency (Cronbach’s alpha = 0.51 and 0.48, respectively). The test/retest reliability ICC = 0.89 and SEm = 1.11, indicating good reliability. The statistical cut-off score for good versus poor adherence was 10, but the clinical cut-off score was found to be 2.Conclusion: This survey tool, OMAS-37 (OsloMet Adherence to medication Survey tool, 37 items), demonstrated to be a valid and reliable instrument for assessing adherence. Further studies will examine the ability of the tool for measuring adherence enhancing effect following interventions.
Repeatability of MRI for radiotherapy planning for pelvic, brain, and head and neck malignancies
Authors: Heinke Monique Y. , Holloway Lois , Rai Robba , Vinod Shalini K. 
Published: December 2022

Objectives: The objective of this study was to assess the repeatability of MRI for the purpose of radiotherapy treatment planning by considering the difference in registering MRI to MRI compared to registering CT and MRI.Methods: Fifty patients undergoing radiotherapy planning for gynaecological, prostate, rectal, head and neck and CNS malignancies had a planning CT followed by two T2-weighted MRIs. Anatomical landmarks were contoured on each dataset and the images were rigidly registered. Centre of Mass (COM), Dice Similarity Coefficient (DSC), and Mean Distance to Agreement (MDA) were calculated to assess structure volume and position comparing CT-MRI and MRI-MRI.Results: DSC and MDA demonstrated more consistency in delineated volumes for MRI-MRI than for the CT-MRI comparison. The median DSC values were ≥0.8 for 15 of 46 contoured structures for the CT-MRI comparison and 21 of 23 structures for the MRI-MRI comparison. MDA values were ≤1 mm for 11 of 46 structures for the CT-MRI comparison and 18 of 23 structures for the MRI-MRI comparisons. COM were also more consistent between MRI-MRI than between CT-MRI.Conclusion: There was less variability of anatomical structures between repeated MRIs than registered CT and MRI datasets, demonstrating consistency of MRI for volume delineation in radiotherapy planning.
Biobehavioral and psychosocial stress changes during three 8–12 month spaceflight analog missions with Mars-like conditions of isolation and confinement
Authors: Dunn Rosenberg Jocelyn , Jannasch Amber , Binsted Kim , Landry Steven 
Published: December 2022

Prior theories about individual and team adaptation to living and working in an isolated and confined environment (ICE) have been derived from the experiences of individuals who winter-over in Antarctica or deploy for long durations in submarines. These theories are typically described as a 3- to 4-stage process with phases of excitement and elevated alertness, then followed by difficult phases, including depression and volatility. To further evaluate the applicability of these theories to long-duration human spaceflight missions, longitudinal stress responses to prolonged isolation and confinement of three 6-person crews during 8–12 months simulated Mars missions were characterized through metabolite profiling (biomarkers in hair and urine samples), wearables monitoring (sleep and activity levels), and self-reported ratings of stress, mood, social participation, and perceived health. These data were normalized, aggregated, and clustered to analyze longitudinal trends in biobehavioral and psychosocial stress measures. As a result, this analysis presents a theoretical model that triangulates aspects of prior theories with new evidence to describe ICE stress at HI-SEAS as 1) eustress of initial adaptation (high stress hormone levels at mission start), 2) deprivation due to prolonged isolation and confinement (decreasing dopamine and serotonin levels), 3) disruption of individual and team dynamics (changes in activity levels, mood, perceived stress, and social participation) and 4) asynchronous coping (changes in sleep-wake cycles, outlook, and team cohesion). These findings support several aspects of prior theories in combination, such as the elevated alertness at mission start and that adverse conditions are most likely to develop after the halfway point of a mission (e.g. for HI-SEAS 8–12 months missions, after approximately 6 months) followed by a period of volatility until the end (e.g. as stated in Rohrer’s theory, ups and downs until the end, not a renewed outlook at the end as described in 3rd quarter phenomenon theory).
Before allyship: A model of integrating awareness of a privileged social identity
Authors: Bergkamp Jude , Olson Lindsay , Martin Abi 
Published: December 2022

IntroductionAlthough the American Psychological Association encourages clinical psychologists to recognize and understand the experience of social privilege both within themselves and the individuals and communities they serve, there is a dearth of research in the field to guide this pursuit. According to the available literature, an essential barrier to social privilege integration is its implicit and covert nature that prevents consistent consciousness due to hegemonic forces.MethodsThis study explored the process, from initial social privilege awareness to the moment of the study, through individual interviews. A social-constructivist, grounded theory approach was utilized as it was aligned with the understudied phenomena oriented around social justice.ResultsThe result is a developmental model of social privilege integration that explicates accumulated exposures to privilege, the resultant threat to and protection of personal identity, and the conducive factors that lead to reconciliation.DiscussionImplications of this theoretical model include the importance of a developmental perspective to cultivate an understanding of individual prejudice attitudes and discriminatory behaviors, as well as a roadmap toward equitable change. This model may be used by clinical psychologists across multiple settings in response to the most recent APA multicultural guidelines.
Motor cortical inhibitory deficits in patients with obsessive-compulsive disorder–A systematic review and meta-analysis of transcranial magnetic stimulation literature
Authors: Rodrigues da Silva Daniel , Maia Ana , Cotovio Gonçalo , Oliveira José , Oliveira-Maia Albino J. , Barahona-Corrêa J. Bernardo 
Published: December 2022

IntroductionObsessive-compulsive disorder (OCD) is a highly prevalent chronic disorder, often refractory to treatment. While remaining elusive, a full understanding of the pathophysiology of OCD is crucial to optimize treatment. Transcranial magnetic stimulation (TMS) is a non-invasive technique that, paired with other neurophysiological techniques, such as electromyography, allows for in vivo assessment of human corticospinal neurophysiology. It has been used in clinical populations, including comparisons of patients with OCD and control volunteers. Results are often contradictory, and it is unclear if such measures change after treatment. Here we summarize research comparing corticospinal excitability between patients with OCD and control volunteers, and explore the effects of treatment with repetitive TMS (rTMS) on these excitability measures.MethodsWe conducted a systematic review and meta-analysis of case-control studies comparing various motor cortical excitability measures in patients with OCD and control volunteers. Whenever possible, we meta-analyzed motor cortical excitability changes after rTMS treatment.ResultsFrom 1,282 articles, 17 reporting motor cortex excitability measures were included in quantitative analyses. Meta-analysis regarding cortical silent period shows inhibitory deficits in patients with OCD, when compared to control volunteers. We found no statistically significant differences in the remaining meta-analyses, and no evidence, in patients with OCD, of pre- to post-rTMS changes in resting motor threshold, the only excitability measure for which longitudinal data were reported.DiscussionOur work suggests an inhibitory deficit of motor cortex excitability in patients with OCD when compared to control volunteers. Cortical silent period is believed to reflect activity of GABAB receptors, which is in line with neuroimaging research, showing GABAergic deficits in patients with OCD. Regardless of its effect on OCD symptoms, rTMS apparently does not modify Resting Motor Threshold, possibly because this measure reflects glutamatergic synaptic transmission, while rTMS is believed to mainly influence GABAergic function. Our meta-analyses are limited by the small number of studies included, and their methodological heterogeneity. Nonetheless, cortical silent period is a reliable and easily implementable measurement to assess neurophysiology in humans, in vivo. The present review illustrates the importance of pursuing the study of OCD pathophysiology using cortical silent period and other easily accessible, non-invasive measures of cortical excitability.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201764], identifier [CRD42020201764].