bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring resource use in Medicare Advantage using Encounter data
Authors: Jung Jeah , Carlin Caroline , Feldman Roger 
Published: September 2021

AbstractObjectiveTo check the completeness of Medicare Advantage (MA) Encounter data and to illustrate a process to measure resource use among MA enrollees using Encounter data.Data sources2015 Preliminary MA Encounter, Medicare Provider Analysis and Review (MedPAR), Healthcare Effectiveness Data and Information System (HEDIS), and 2013 Traditional Medicare (TM) claims data.Study designSecondary data analysis.Data collection/extraction methodsWe calculated the percentage of each contract's total hospitalizations in Encounter data after identifying total inpatient stays from Encounter and MedPAR data. We constructed each contract's ambulatory visits and emergency department (ED) visits per 1000 enrollees using Encounter data and compared those visit counts with the counts from HEDIS. We defined high data completeness as having less than 10% missing hospital stays and less than ±10% difference in ambulatory and ED visits between Encounter and HEDIS data. We used TM payments as standardized prices of services to examine resource use among MA enrollees with cancer in the contracts with high data completeness.Principal findingsWe identified 83 of 380 MA contracts with high data completeness. Total resource use per enrollee with cancer in the 83 contracts was $14,715 in 2015. Service‐specific resource use was $5342 for inpatient care, $5932 for professional services and $3441 for outpatient facility services. These represent what an MA enrollee with cancer would have cost on average if MA plans paid providers at TM payment rates, holding the observed utilization constant.ConclusionsChecking the completeness of Encounter data is an important step to ensure the validity of research on MA resource use. Using Encounter data to measure MA resource use is feasible. It can compensate for the lack of payment information in Encounter data. It will be important to identify and refine ways to best use Encounter data to learn about care provision to MA enrollees.
18F‐FET PET maximum standard uptake value and WHO tumour classification grade in glioma
Authors: Tatkovic Annaleis , McBean Rhiannon , Perkins Ebony , Wong David 
Published: September 2021

AbstractBackgroundIn the area of oncology, molecular imaging techniques are becoming increasingly utilised. In neuro‐oncology imaging, 18Fluoro‐O‐(2) fluoroethyl‐L‐tyrosine (18F‐FET) is one of the molecular tracers used in positron‐emission tomography (PET). Here, we investigated the correlation between maximum standard uptake value (SUV) of 18F‐FET PET and histologically determined World Health Organization (WHO) grade in glioma.Patients and MethodsThis was a retrospective review of all 18F‐FET PET studies conducted between August 2014 and August 2019. Review was conducted to identify imaging studies performed on patients who had a glioma with histopathology results from surgical resection or biopsy available.ResultsA total of 31 18F‐FET PET studies of histologically confirmed glioma were included. WHO grades ranged from II‐IV. A positive correlation between maximum SUV uptake on 18F‐FET PET and WHO grade was observed.ConclusionsThere was a correlation identified between WHO glioma grade and maximum SUV on 18F‐FET PET. Further studies are recommended to explore this relationship.
Genetic and immune characteristics of multiple primary lung cancers and lung metastases
Authors: Yang Ronghua , Li Peng , Wang Dong , Wang Lingjie , Yin Jihui , Yu Baohua , Li Mengjun , Wang Sai , Wang Yongjie 
Published: September 2021

AbstractBackgroundTo explore the genetic and immunophenotyping heterogeneities between patients with intrapulmonary metastasis (IPM) or multiple primary lung cancer (MPLC).MethodsWhole exome sequencing (WES) and transcriptome sequencing (RNA‐seq) were performed on the tissue and blood samples of IPM and MPLC patients to comprehensively analyze the clonal evolution, molecular typing and immunophenotyping.ResultsThere was no significant difference in genetic mutation, tumor mutational burden (TMB) value and mutant allele tumor heterogeneity (MATH) value between IPM and MPLC patients. Notably, the loss of heterozygosity (LOH) of human leukocyte antigen (HLA) appeared in all IPM patients, while there was also no significant difference between the two groups. In addition, expression of immune checkpoint‐related genes including CTLA‐4, BTLA, TIGIT and HAVCR2 in the MPLC group was significantly higher than those in IPM group. At the same time, 86 differentially expressed genes (DEGs) were observed between IPM and MPLC patients with transcriptome sequencing, of which 56 DEGs were upregulated and 30 were downregulated in the IPM group compared with the MPLC group. The cluster analysis revealed that the 86 DEGs could be distinguished in IPM and MPLC samples. Moreover, only the infiltration levels of CD56dim natural killer cells in the IPM group was significantly higher than that in the MPLC group, and the infiltration levels of the remaining 27 immune cell subsets were similar in both groups.ConclusionsIPM and MPLC are roughly similar in genetic and immune characteristics indicating that genomics alone may not be able to effectively distinguish between IPM and MPLC, which still needs to be comprehensively evaluated with clinical manifestations, imaging, and pathological characteristics.
The Effect of SEC Reviewers on Comment Letters*
Authors: Baugh Matthew , Kim Kyonghee , Lee Kwang J. 
Published: September 2021

ABSTRACTPrior research suggests that even for the same decision task there will be variation in decision outcomes across decision makers due to idiosyncrasies in their styles. This variation brings up a fundamental challenge in the realm of regulations, where consistency of application is of great importance. This study examines whether the idiosyncrasies of individual employees of the SEC contribute to inconsistent regulatory outcomes. Using a sample of SEC comment letters, we show that SEC reviewers' idiosyncratic style plays a significant role in explaining the cross‐sectional variation in filing review outcomes, even after holding firm and disclosure attributes constant. In addition, the likelihood of restatement during the review process varies systemically with the reviewers' review style. These findings suggest that reviewer style influences shareholders and other stakeholders via its impact on the costs in resolving comment letter issues and the quality of corporate disclosure. They also have public policy implications for the way financial reporting rules and regulations are applied.
microRNA‐425 loss mediates amyloid plaque microenvironment heterogeneity and promotes neurodegenerative pathologies
Authors: Hu Yong‐Bo , Zhang Yong‐Fang , Ren Ru‐Jing , Dammer Eric B. , Xie Xin‐Yi , Chen Shi‐Wu , Huang Qiang , Huang Wan‐Ying , Zhang Rui , Chen Hong‐Zhuan , Wang Hao , Wang Gang 
Published: September 2021

AbstractDifferent cellular and molecular changes underlie the pathogenesis of Alzheimer's disease (AD). Among these, neuron‐specific dysregulation is a necessary event for accumulation of classic pathologies including amyloid plaques. Here, we show that AD‐associated pathophysiology including neuronal cell death, inflammatory signaling, and endolysosomal dysfunction is spatially colocalized to amyloid plaques in regions with abnormal microRNA‐425 (miR‐425) levels and this change leads to focal brain microenvironment heterogeneity, that is, an amyloid plaque‐associated microenvironment (APAM). APAM consists of multiple specific neurodegenerative signature pathologies associated with senile plaques that contribute to the heterogeneity and complexity of AD. Remarkably, miR‐425, a neuronal‐specific regulator decreased in AD brain, maintains a normal spatial transcriptome within brain neurons. We tested the hypothesis that miR‐425 loss correlates with enhanced levels of mRNA targets downstream, supporting APAM and AD progression. A miR‐425‐deficient mouse model has enhanced APP amyloidogenic processing, neuroinflammation, neuron loss, and cognitive impairment. In the APP/PS1 mouse model, intervening with miR‐425 supplementation ameliorated APAM changes and memory deficits. This study reveals a novel mechanism of dysregulation of spatial transcriptomic changes in AD brain, identifying a probable neuronal‐specific microRNA regulator capable of staving off amyloid pathogenesis. Moreover, our findings provide new insights for developing AD treatment strategies with miRNA oligonucleotide(s).
Brain age in mood and psychotic disorders: a systematic review and meta‐analysis
Authors: Ballester Pedro L. , Romano Maria T. , de Azevedo Cardoso Taiane , Hassel Stefanie , Strother Stephen C. , Kennedy Sidney H. , Frey Benicio N. 
Published: September 2021

AbstractObjectiveTo evaluate whether accelerated brain aging occurs in individuals with mood or psychotic disorders.MethodsA systematic review following PRISMA guidelines was conducted. A meta‐analysis was then performed to assess neuroimaging‐derived brain age gap in three independent groups: (1) schizophrenia and first‐episode psychosis, (2) major depressive disorder, and (3) bipolar disorder.ResultsA total of 18 papers were included. The random‐effects model meta‐analysis showed a significantly increased neuroimaging‐derived brain age gap relative to age‐matched controls for the three major psychiatric disorders, with schizophrenia (3.08; 95%CI [2.32; 3.85]; p < 0.01) presenting the largest effect, followed by bipolar disorder (1.93; [0.53; 3.34]; p < 0.01) and major depressive disorder (1.12; [0.41; 1.83]; p < 0.01). The brain age gap was larger in older compared to younger individuals.ConclusionIndividuals with mood and psychotic disorders may undergo a process of accelerated brain aging reflected in patterns captured by neuroimaging data. The brain age gap tends to be more pronounced in older individuals, indicating a possible cumulative biological effect of illness burden.
Changes in interoception after alcohol administration correlate with expectancies and subjective effects
Authors: Leganes‐Fonteneau Mateo , Bates Marsha E. , Islam Shahriar , Buckman Jennifer F. 
Published: September 2021

AbstractInteroceptive signals give rise to subjective feeling states that can drive motivational and behavioural responses. In the context of alcohol use behaviours, interoceptive signals may shape subjective alcohol experiences and thereby support biobehavioural mechanisms of drinking behaviour change. This study examined the acute effects of alcohol on participants' interoceptive abilities and determined whether pharmacologically induced changes in heart beat detection correlate with subjective alcohol effects, craving and expectancies. Participants completed a two‐session, double‐blind placebo controlled experiment (n = 27). Participants consumed a beverage containing 0.4 g/kg of alcohol or a placebo. They also completed measurements of alcohol expectancies at baseline, and alcohol‐induced changes in mood, craving and light‐headedness. Interoceptive ability was measured using the heartbeat discrimination task prior to and following beverage administration, yielding indices of interoceptive accuracy, confidence and meta‐cognition. Alcohol administration increased interoceptive accuracy compared with baseline and placebo; and those changes in interoception negatively correlated with negative alcohol expectancies. Further, changes in interoception positively correlated with perceived light‐headedness and positive mood after alcohol administration, whereas null effects were found for craving. In the placebo condition, null results were obtained. Alcohol is well established to change bodily states, and here, we find that the extent to which alcohol increases participants' sensitivity to bodily states correlates with their subjective drinking experiences. This was observed in relation to mood, light‐headedness and prospective alcohol expectancies. We posit that over successive alcohol experiences, changes in bodily states may feed into the development of alcohol expectancies that could in turn predict future drinking behaviours.
Ultrasonography of the gastrointestinal tract of toco toucans (Ramphastos toco)
Authors: da Silva Jeana Pereira , Rahal Sheila Canevese , Castiglioni Maria Cristina Reis , Rolim Luna Scarpari , Lima Whítara Ferreira , Schimming Bruno Cesar , Moresco Anneke , Mamprim Maria Jaqueline 
Published: September 2021

AbstractBaseline data for wall thickness in healthy toucans can be used to diagnose disease in sick individuals. This study aimed to evaluate the use of ultrasonography for the examination of the gastrointestinal tract of healthy toco toucans (Ramphastos toco). Ten non‐anaesthetized healthy adult toco toucans were evaluated. Food was withheld for 3 h prior to the ultrasound examination. Longitudinal and transverse images of the gastrointestinal tract were obtained using ventromedian cranial and ventromedian caudal approaches to evaluate the morphology and stratification. The wall thickness of the sections was measured: proventriculus and ventriculus, duodenum, jejunum/ileum, and cloaca. Additionally, the thickness of the mucosal layer of the duodenum and jejunum/ileum was also measured. Subsequently, the ratios of the duodenal wall thickness to the duodenal mucosa layer and the total wall thickness of the jejunum/ileum to the jejunum/ileum layer mucosa were stablished. The wall thickness of the proventriculus was significantly higher than the wall thickness of ventriculus. The wall thickness of the duodenum was significantly higher than the wall thickness of jejunum/ileum. The mean ratios of the duodenal wall thickness to the duodenal mucosa layer and the wall thickness of the jejunum/ileum to the jejunum/ileum layer were 83.15% and 80.07%, respectively. In conclusion, it was possible to assess the stomach and intestines using ultrasound examination in healthy toco toucans, due to their medium body size and no interference by surrounding air sacs.
Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age
Authors: Pastuszak Alexander W. , Gittelman Marc , Tursi James P. , Jaffe Jonathan S. , Schofield David , Miner Martin M. 
Published: September 2021

AbstractBackgroundTo improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations.ObjectiveTo compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age.Materials and methodsA literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed.Discussion and conclusionEndogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.
Humanitarian Capture, Solidarity’s Excess: Affect, Experience, and the Mobile Commons in Migrant Solidarity
Authors: Ramírez March Álvaro 
Published: September 2021

AbstractThis article focuses on the relation of affect and the mobile commons by drawing on the case of migrant solidarity in the Spanish state during the so‐called “refugee crisis”. I begin by portraying the context of emergence of migrant solidarity in Catalonia and its relation to the “humanitarian affective governmentality” (HAG) of both migrants and their supporters—a regime that redirects affects in collective organising to reinforce European borders. Despite these attempts of co‐option, however, I argue that migrant solidarity may exceed the capture from HAG. Excess refers, in a first instance, to the role of affects in the social production of experience; and in a second instance, to how collective organising feeds the virtuality that freedom of movement is still possible. I thus argue for the consideration of affects, understood as that emerging in the encounters between bodies, as part of the mobile commons.
Meta‐analysis found high rates of post‐traumatic stress disorder and associated risk factors in parents following paediatric medical events
Authors: Burgess Aaron , Wilcoxon Lucy , Rushworth Imogen , Meiser‐Stedman Richard 
Published: September 2021

AbstractAimThis meta‐analysis identified how prevalent parental post‐traumatic stress disorder (PTSD) was after their children's medical events and evaluated the risk factors that increased the likelihood of PTSD.MethodsThe MEDLINE, PsycINFO and PTSDpubs databases were searched for papers published in English from 1980 to June 2018. The prevalence of parental PTSD was pooled across the studies and risk factors were extracted whether PTSD symptoms were correlated with other research variables or when the authors had conducted between group analyses of PTSD. We also explored the effects of the assessment method, parental gender and medical events and the risk of bias.ResultsThe 54 studies that were identified had a pooled PTSD prevalence rate of 30.3% (95% confidence interval 25.3%–35.5%). Childhood cancer cases yielded the highest rates of parental PTSD. A total of 33 potential risk factors were identified. The risk factors with medium to large effects were: comorbid parental psychological responses and functioning, acute stress responses, child behavioural functioning, uncertainty about the child's illness and negative coping strategies. The findings are discussed within the context of high heterogeneity.ConclusionThe prevalence of parental PTSD after paediatric medical events was relatively high, and 33 risk factors were identified.
Discussion on “Causal mediation of semicompeting risks” by Yen‐Tsung Huang
Authors: Fulcher Isabel R. , Shpitser Ilya , Didelez Vanessa , Zhou Kali , Scharfstein Daniel O. 
Published: September 2021

AbstractHuang proposes a method for assessing the impact of a point treatment on mortality either directly or mediated by occurrence of a nonterminal health event, based on data from a prospective cohort study in which the occurrence of the nonterminal health event may be preemptied by death but not vice versa. The author uses a causal mediation framework to formally define causal quantities known as natural (in)direct effects. The novelty consists of adapting these concepts to a continuous‐time modeling framework based on counting processes. In an effort to posit “scientifically interpretable estimands,” statistical and causal assumptions are introduced for identification. In this commentary, we argue that these assumptions are not only difficult to interpret and justify, but are also likely violated in the hepatitis B motivating example and other survival/time to event settings as well.
SCRUM‐Japan GI‐SCREEN and MONSTAR‐SCREEN: Path to the realization of biomarker‐guided precision oncology in advanced solid tumors
Authors: Nakamura Yoshiaki , Fujisawa Takao , Taniguchi Hiroya , Bando Hideaki , Okamoto Wataru , Tsuchihara Katsuya , Yoshino Takayuki , Ohtsu Atsushi 
Published: September 2021

AbstractComprehensive genomic profiling enables the detection of genomic biomarkers in advanced solid tumors. However, efficient patient screening for the success of precision oncology remains challenging due to substantial barriers, such as genotyping costs and accessibility to matched therapies. To address these challenges, we launched GI‐SCREEN, a nationwide gastrointestinal cancer genomic screening project within the SCRUM‐Japan network in 2015 with the specific purpose of matching patients with a diverse portfolio of affiliated interventional targeted therapy trials. Subsequently, we initiated the molecular profiling projects GOZILA, MONSTAR‐SCREEN‐1, and MONSTAR‐SCREEN‐2, which incorporate tissue and plasma multiomics approaches to accurately identify patients with advanced solid tumors who would benefit from matched therapies. These projects have led to a significant increase in patient participation in targeted clinical trials and the approval of several therapeutics and companion diagnostics. Additionally, clinicogenomic analyses utilizing the SCRUM‐Japan database have provided new insights into the molecular mechanisms of advanced solid tumors. In this review, we describe the path to the realization of cancer precision medicine for patients with advanced solid tumors based on the SCRUM‐Japan GI‐SCREEN and MONSTAR‐SCREEN platforms.
Emerging treatment evolutions and integrated molecular characteristics of biliary tract cancers
Authors: Zhang Ruyi , Puzzoni Marco , Mariani Stefano , Zheng Yi , Liscia Nicole , Guo Yixuan , Donisi Clelia , Liu Yu , Impera Valentino , Fang Weijia , Scartozzi Mario 
Published: September 2021

AbstractBiliary tract cancers (BTCs) consist of a group of highly heterogeneous malignancies that are characterized by genomic differences among tumors from different anatomic sites. The current treatment for BTC includes surgery, chemotherapy, target therapy, and immunotherapy. Although surgery remains the primary option for localized disease, representing the only potential curative treatment, a high risk of recurrence cannot be neglected. Chemotherapy has been considered the standard of care for both advanced and metastatic disease and in adjuvant settings. However, drug resistance is a major obstacle associated with chemotherapy. The development of genetic testing technologies, including next‐generation sequencing, has opened the door for the identification of drug targets and candidate molecules. A series of preclinical studies has demonstrated the role of gene mutations, abnormal signaling pathways, and immunosuppression in the pathogenesis of BTC, laying the foundation for the application of targeted therapy and immunotherapy. A variety of molecularly targeted agents, including pemigatinib, have shown promising survival benefits in patients with advanced disease. The rapidly evolving role of multimodal therapy represents the subject of this review.
Children boost their cognitive performance with a novel offloading technique
Authors: Armitage Kristy L. , Redshaw Jonathan 
Published: September 2021

AbstractNinety‐seven children aged 4–11 (49 males, 48 females, mostly White) were given the opportunity to improve their problem‐solving performance by devising and implementing a novel cognitive offloading strategy. Across two phases, they searched for hidden rewards using maps that were either aligned or misaligned with the search space. In the second phase, maps were presented on rotatable turntables, thus allowing children to manually align all maps and alleviate mental rotation demand. From age six onwards, children showed strong evidence of both mentally rotating misaligned maps in phase 1 and manually aligning them in phase 2. Older children used this form of cognitive offloading more frequently, which substantially improved performance and eliminated the individual differences observed in phase 1.