bluuebunny/crossref_metadata_2025_split huggingface dataset:
ImmunoPET Imaging with 89Zr-Labeled Atezolizumab Enables In Vivo Evaluation of PD-L1 in Tumorgraft Models of Renal Cell Carcinoma
Authors: Mulgaonkar Aditi , Elias Roy , Woolford Layton , Guan Bing , Nham Kien , Kapur Payal , Christie Alana , Tcheuyap Vanina T. , Singla Nirmish , Bowman I. Alex , Stevens Christina , Hao Guiyang , Brugarolas James , Sun Xiankai 
Published: September 2022

Abstract

Purpose:
Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 and its ligand (PD-1/PD-L1) have transformed the treatment paradigm for metastatic renal cell carcinoma (RCC). However, response rates to ICIs as single agents or in combination vary widely and predictive biomarkers are lacking. Possibly related to the heterogeneity and dynamic nature of PD-L1 expression, tissue-based methods have shown limited value. Immuno–positron emission tomography (immunoPET) may enable noninvasive, comprehensive, and real-time PD-L1 detection. Herein, we systematically examined the performance of immunoPET for PD-L1 detection relative to IHC in an RCC patient-derived tumorgraft (TG) platform.

Experimental Design:
Eight independent RCC TGs with a wide range of PD-L1 expression (0%–85%) were evaluated by immunoPET. Uptake of 89Zr-labeled atezolizumab ([89Zr]Zr-DFO-ATZ) was compared with PD-L1 expression in tumors by IHC through double-blind analyses. Clinical outcomes of ICI-treated patients whose TGs were examined were analyzed to evaluate the clinical role of immunoPET in RCC.

Results:
ImmunoPET with [89Zr]Zr-DFO-ATZ (day 6/7 postinjection) revealed a statistically significant association with PD-L1 IHC assays (P = 0.0014; correlation ρXY = 0.78). Furthermore, immunoPET can be used to assess the heterogeneous distribution of PD-L1 expression. Finally, studies in the corresponding patients (n = 4) suggest that PD-L1 signal may influence ICI responsiveness.

Conclusions:
ImmunoPET with [89Zr]Zr-DFO-ATZ may enable a thorough and dynamic assessment of PD-L1 across sites of disease. The power of immunoPET to predict ICI response in RCC is being explored in an ongoing clinical trial (NCT04006522).
Liquid Biopsy Detects Early Molecular Response and Predicts Benefit to First-Line Chemotherapy plus Cetuximab in Metastatic Colorectal Cancer: PLATFORM-B Study
Authors: Vidal Joana , Fernández-Rodríguez Maria Concepción , Casadevall David , García-Alfonso Pilar , Páez David , Guix Marta , Alonso Vicente , Cano Maria Teresa , Santos Cristina , Durán Gema , Elez Elena , Manzano José Luís , Garcia-Carbonero Rocío , Ferreiro Reyes , Losa Ferran , Pineda Estela , Sastre Javier , Rivera Fernando , Bellosillo Beatriz , Tabernero Josep , Aranda Enrique , Salazar Ramon , Montagut Clara ,   on behalf of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Published: September 2022

Abstract

Purpose:
Chemotherapy plus anti-EGFR is standard first-line therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC), but biomarkers of early response are clinically needed. We aimed to define the utility of ctDNA to assess early response in patients with mCRC receiving first-line anti-EGFR therapy.

Experimental Design:
Prospective multicentric study of tissue patients with RAS wt mCRC treated with first-line chemotherapy plus cetuximab undergoing sequential liquid biopsies. Baseline and early (C3) ctDNA were analyzed by NGS. Trunk mutations were assessed as surrogate marker of total tumor burden. RAS/BRAF/MEK/EGFR-ECD were considered mutations of resistance. ctDNA results were correlated with clinical outcome.

Results:
One hundred patients were included. ctDNA was detected in 72% of patients at baseline and 34% at C3. Decrease in ctDNA trunk mutations correlated with progression-free survival (PFS; HR, 0.23; P = 0.001). RAS/BRAF were the only resistant mutations detected at C3. An increase in the relative fraction of RAS/BRAF at C3 was followed by an expansion of the RAS clone until PD, and was associated with shorter PFS (HR, 10.5; P &lt; 0.001). The best predictor of response was the combined analysis of trunk and resistant mutations at C3. Accordingly, patients with “early molecular response” (decrease in trunk and decrease in resistant mutations) had better response (77.5% vs. 25%, P = 0.008) and longer PFS (HR, 0.18; P &lt; 0.001) compared with patients with “early molecular progression” (increase in trunk and/or increase in resistant mutations).

Conclusions:
ctDNA detects early molecular response and predicts benefit to chemotherapy plus cetuximab. A comprehensive NGS-based approach is recommended to integrate information on total disease burden and resistant mutations.
See related commentary by Eluri et al., p. 302
TFAP4 Activates IGF2BP1 and Promotes Progression of Non–Small Cell Lung Cancer by Stabilizing TK1 Expression through m6A Modification
Authors: Shen Qiming , Xu Zhe , Sun Guanghao , Wang Haoyou , Zhang Lin 
Published: September 2022

Abstract

Non–small cell lung cancer (NSCLC) is a well-known global health concern. TFAP4 has been reported to function as an oncogene. This study sought to investigate the molecular mechanism of TFAP4 in NSCLC development. Significantly highly-expressed gene IGF2BP1 was screened on online databases and its downstream gene TK1 was predicted. IGF2BP1 promoter sequence was identified. The binding site of TFAP4 and IGF2BP1 was predicted. The expression correlations among TFAP4, IGF2BP1, and TK1 were confirmed. The correlations between TFAP4, IGF2BP1, TK1, and NSCLC prognosis were predicted. NSCLC and paracancerous tissues were collected. The expressions of TFAP4, IGF2BP1, and TK1 were detected. NSCLC cell proliferation, migration, invasion, and apoptosis were detected. The binding of TFAP4 to the IGF2BP1 promoter was verified. m6A modification of TK1 mRNA was detected. The correlation between IGF2BP1 and TK1 was confirmed. A subcutaneous tumor xenograft model was established to validate the effect of TFAP4 in vivo. IGF2BP1 was highly expressed in NSCLC tissues and cells. IGF2BP1 knockdown repressed NSCLC cell proliferation, migration, and invasion and facilitated apoptosis. Mechanically, TFAP4 transcriptionally activated IGF2BP1. IGF2BP1 stabilized TK1 expression via m6A modification and promoted NSCLC cell proliferation, migration, and invasion. In vivo experiments confirmed that TFAP4 knockdown suppressed tumor growth by downregulating IGF2BP1/TK1.

Implications:
Our findings revealed that TFAP4 activated IGF2BP1 and facilitated NSCLC progression by stabilizing TK1 expression via m6A modification, which offered new insights into the diagnosis and treatment of NSCLC.
Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake
Authors: Yoshida Naohisa , Ishikawa Hideki , Otani Takahiro , Goto Chiho , Matsuda Takahisa , Takeuchi Yoji , Sano Yasushi , Itoh Yoshito , Suzuki Sadao , Mutoh Michihiro ,   on behalf of the J-CAPP Study group
Published: September 2022

Abstract

Aspirin has been shown to prevent the onset of colorectal adenoma and cancer. This study aimed to identify patient characteristics and blood chemistry factors related to the effect of aspirin. A total of 231 men and 59 women who participated in our previous randomized clinical study in 2007–2009 using aspirin or placebo (J-CAPP study) were analyzed. Interaction of aspirin with age at entry, body mass index (BMI), alcohol intake, blood biochemistry, and nutrients calculated from a semiquantitative food frequency questionnaire were analyzed on the basis of the presence of adenomas 2 years later. Our study showed that suppression of adenoma by aspirin was not affected by age or BMI. Among men, significant suppression of adenoma by aspirin was seen with triglyceride (TG) &lt;167 mg/dL (P = 0.02), total cholesterol (T-cho) ≥220 mg/dL (P = 0.01), high-density lipoprotein (HDL) ≥60 mg/dL (P &lt; 0.01), and low-density lipoprotein (LDL) ≥140 mg/dL (P = 0.01), aspartate aminotransferase (AST) &lt;30 IU/L (P = 0.01), alanine aminotransferase &lt;30 IU/L (P = 0.04), and gamma-glutamyl transpeptidase &lt;60 IU/L (P = 0.04). In addition, the interaction was significant with TG ≥/&lt;167 mg/dL (P = 0.02), T-cho ≥/&lt;220 mg/dL (P = 0.03), HDL ≥/&lt;60 mg/dL (P = 0.02), LDL ≥/&lt;140 mg/dL (P = 0.03), and AST ≥/&lt;30 IU/L (P = 0.01). Daily nutrient intake associated with aspirin was &lt;2,000 mg sodium (P = 0.06) and ≥850 μg retinol equivalent (P = 0.05) among men, indicating a marginal effect on adenoma suppression. No significant differences were detected among women due to the small sample size. In conclusion, lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.

Prevention Relevance:
Aspirin has been shown to prevent the onset of colorectal adenoma and cancer, and its effect modifications have been analyzed. Lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.
Coronary Artery Restenosis in Women by History of Preeclampsia
Authors: Lin Annie , Pehrson Moa , Sarno Giovanna , Fraser Abigail , Rich‐Edwards Janet W. , Gonҫalves Isabel , Pihlsgård Mats , Timpka Simon 
Published: September 2022

Background
A history of preeclampsia is associated with increased risk of coronary artery disease and experimental evidence suggests that a history of preeclampsia also increases the risk of restenosis. However, the extent to which a history of preeclampsia is associated with risk of restenosis after percutaneous coronary intervention in women is unknown.

Methods and Results
We included 6065 parous women aged ≤65 years with first percutaneous coronary intervention on 9452 segments 2006 to 2017, linking nationwide data on percutaneous coronary intervention and delivery history in Sweden. Main outcomes were clinical restenosis and target lesion revascularization within 2 years. We accounted for segment‐, procedure‐, and patient‐related potential predictors of restenosis in proportional hazards regression models. Restenosis occurred in 345 segments (3.7%) and target lesion revascularization was performed on 383 patients (6.3%). A history of preeclampsia was neither significantly associated with risk of restenosis (predictor‐accounted hazard ratio [HR], 0.71 [95% CI, 0.41–1.23]) nor target lesion revascularization (0.74 [95% CI, 0.51–1.07]) compared with a normotensive pregnancy history. When term and preterm preeclampsia were investigated separately, segments in women with a history of term preeclampsia had a lower risk of restenosis (predictor‐accounted HR, 0.45 [95% CI, 0.21–0.94]). A history of preeclampsia was not significantly associated with death by any cause within 2 years of the index procedure (predictor‐accounted HR 1.06, [95% CI, 0.62–1.80]).

Conclusions
A history of preeclampsia was not associated with increased risk of restenosis but instead some evidence pointed to a decreased risk. To facilitate future studies and allow for replication, concomitant collection of data on pregnancy complication history and percutaneous coronary intervention outcomes in women is warranted.
Endovascular Therapy of Tandem Occlusions: Baseline Characteristics and Outcomes Compared With Intracranial Occlusion
Authors: Sørensen Mads M. , Leslie‐Mazwi Thabele M. , Jensen Jonas , Valentin Jan B. , Simonsen Claus Z. 
Published: September 2022

Background
Endovascular therapy is highly effective in stroke caused by large vessel occlusion. Guidelines support treatment in case of occlusion of the intracranial internal carotid artery or the first segment of the middle cerebral artery. We aimed to examine baseline characteristics and outcome of patients who underwent endovascular therapy for tandem occlusions.

Methods
We conducted a retrospective study of patients who underwent endovascular therapy of tandem occlusion or occlusion of intracranial internal carotid artery/first segment of the middle cerebral artery between May 2015 and December 2019. Univariate comparisons of baseline characteristics and outcome (favorable functional outcome 90‐days after treatment and mortality) were performed. We used inverse‐probability‐of‐treatment‐weights to adjust for confounders.

Results

We compared 167 patients with tandem occlusion and 414 with intracranial occlusions. Patients with tandem occlusion were younger (69 years [interquartile range: 59.25–76] versus 74 [interquartile range: 64–81];
P
= 0.0002), male (64.7% versus 51.4%;
P
= 0.004), more frequently active smokers (42.5% versus 25.6%;
P
= 0.0001), and less frequently subject to atrial fibrillation (18.6% versus 41.3%;
P
<0.0001). No significant differences were seen in the rate of 90‐day good outcome (49.1% versus 51.0%;
P
= 0.68) or mortality (16.8% versus 18.1%;
P
= 0.70). This was also true after adjustment (relative risk for poor outcome 0.86 [95% CI: 0.72–1.05]). More proximal occlusions resulted in worse outcome in both tandem and intracranial occlusions.

Conclusion
Patients with tandem occlusion were more frequently younger, male smokers without atrial fibrillation illustrating the different risk factors underlying these strokes. Benefit from treatment was similar between groups, supporting endovascular therapy in tandem occlusions.
Dimensional Modeling of Emotions in Text with Appraisal Theories: Corpus Creation, Annotation Reliability, and Prediction
Authors: Troiano Enrica , Oberländer Laura , Klinger Roman 
Published: September 2022

AbstractThe most prominent tasks in emotion analysis are to assign emotions to texts and to understand how emotions manifest in language. An important observation for natural language processing is that emotions can be communicated implicitly by referring to events alone, appealing to an empathetic, intersubjective understanding of events, even without explicitly mentioning an emotion name. In psychology, the class of emotion theories known as appraisal theories aims at explaining the link between events and emotions. Appraisals can be formalized as variables that measure a cognitive evaluation by people living through an event that they consider relevant. They include the assessment if an event is novel, if the person considers themselves to be responsible, if it is in line with their own goals, and so forth. Such appraisals explain which emotions are developed based on an event, for example, that a novel situation can induce surprise or one with uncertain consequences could evoke fear. We analyze the suitability of appraisal theories for emotion analysis in text with the goal of understanding if appraisal concepts can reliably be reconstructed by annotators, if they can be predicted by text classifiers, and if appraisal concepts help to identify emotion categories. To achieve that, we compile a corpus by asking people to textually describe events that triggered particular emotions and to disclose their appraisals. Then, we ask readers to reconstruct emotions and appraisals from the text. This set-up allows us to measure if emotions and appraisals can be recovered purely from text and provides a human baseline to judge a model’s performance measures. Our comparison of text classification methods to human annotators shows that both can reliably detect emotions and appraisals with similar performance. Therefore, appraisals constitute an alternative computational emotion analysis paradigm and further improve the categorization of emotions in text with joint models.
Adapting to the Long Tail: A Meta-Analysis of Transfer Learning Research for Language Understanding Tasks
Authors: Naik Aakanksha , Lehman Jill , Rosé Carolyn 
Published: September 2022

Abstract
Natural language understanding (NLU) has made massive progress driven by large benchmarks, but benchmarks often leave a long tail of infrequent phenomena underrepresented. We reflect on the question: Have transfer learning methods sufficiently addressed the poor performance of benchmark-trained models on the long tail? We conceptualize the long tail using macro-level dimensions (underrepresented genres, topics, etc.), and perform a qualitative meta-analysis of 100 representative papers on transfer learning research for NLU. Our analysis asks three questions: (i) Which long tail dimensions do transfer learning studies target? (ii) Which properties of adaptation methods help improve performance on the long tail? (iii) Which methodological gaps have greatest negative impact on long tail performance? Our answers highlight major avenues for future research in transfer learning for the long tail. Lastly, using our meta-analysis framework, we perform a case study comparing the performance of various adaptation methods on clinical narratives, which provides interesting insights that may enable us to make progress along these future avenues.
Default Grapheme and Language Transfer in the Spelling of /s/ in Spanish Heritage Language Learners
Authors: Llombart-Huesca Amàlia 
Published: September 2022

Abstract
This study investigates the spelling proficiency of Spanish heritage language learners (SHLLs) in the Spanish phoneme-grapheme correspondence that has been identified as the source of the greatest number of spelling errors: /s/ → s, c, z. Using a naturalistic corpus, this study aims to ascertain whether (1) s is SHLL’s default grapheme in the representation of /s/; (2) cognate status is a facilitative factor in spelling; and (3) previous Spanish language instruction affects individual performance in the spelling of /s/. The results show that the preference for s is mediated by difficulties with the c/z alternation and poor spelling in z words. In addition, cognate status was shown to have a facilitative effect in the three relevant graphemes. Finally, the results indicate that one or more years of previous language instruction in secondary school make a statistically significant difference, but that additional Spanish instruction beyond two years did not bring corresponding gains. The results of this study contribute to the scarce literature in Spanish spelling in this population and have pedagogical implications for orthographic patterns that merit particular instructional focus, as well as for strategies that take full advantage of cognates (including semi-cognates and false cognates) in spelling instruction.
The Impact of Topography on the Environment and Life Cycle of Weakly and Strongly Forced MCSs during RELAMPAGO
Authors: Rocque Marquette N. , Rasmussen Kristen L. 
Published: September 2022

Abstract
Intense deep convection and large mesoscale convective systems (MCSs) are known to occur downstream of the Andes in subtropical South America. Deep convection is often focused along the Sierras de Córdoba (SDC) in the afternoon and then rapidly grows upscale and moves to the east overnight. However, how the Andes and SDC impact the life cycle of MCSs under varying synoptic conditions is not well understood. Two sets of terrain-modification experiments using WRF are used to investigate the impact of topography in different synoptic regimes. The first set is run on the 13–14 December 2018 MCS case from RELAMPAGO, which featured a deep synoptic trough, strong lee cyclogenesis near the SDC, an enhanced low-level jet, and rapid upscale growth of an MCS. When the Andes are reduced by 50%, the lee cyclone and low-level jet that develop are weaker than with the full Andes, and the resulting MCS is weak and moves faster to the east. When the SDC are removed, few differences between the environment and resulting MCS relative to the control run are seen. A second set of experiments are run on the 25–26 January 2019 case in which a large MCS developed over the SDC and remained tied there for an extended period under weak synoptic forcing. The experiment that produces the most similar MCS to the control is when the Andes are reduced by 50% while maintaining the height of the SDC, suggesting the SDC may play a more important role in the MCS life cycle under quiescent synoptic conditions.
COVID-19–Related Stressors and Mental Health Disorders Among US Adults
Authors: Coley Rebekah Levine , Carey Naoka , Baum Christopher F. , Hawkins Summer Sherburne 
Published: September 2022

Objectives: The COVID-19 pandemic has led to severe mental health repercussions. We examined rates of anxiety and depression in the United States during the pandemic by demographic characteristics, individual stressors, and COVID-19 infection rates and policy contexts. Methods: We merged data from the April 2020–March 2021 US Household Pulse Survey with state-level data on COVID-19 rates and mitigation policies, including stay-at-home orders, face mask mandates, and restaurant closures. We estimated weighted logistic regression models to assess correlates of anxiety and depression. Results: Rates of anxiety and depression peaked in late 2020 at 39% and 32%, respectively. Food insecurity and disrupted medical care were associated with more than twice the odds of anxiety and depression (food insecurity: odds ratio [OR] = 2.58 for anxiety and 2.61 for depression; disrupted medical care: OR = 2.40 and 2.27). Being not employed (OR = 1.32 for anxiety and 1.45 for depression), uninsured (OR = 1.30 and 1.38), housing insecure (OR = 1.41 and 1.34), and experiencing disruptions in education (OR = 1.28 and 1.25) were linked to 25% to 45% increased odds of anxiety and depression. Increases in state COVID-19 infection rates were associated with significantly heightened odds of anxiety and depression (OR = 1.01 for anxiety and depression), but state mitigation policies were not. Conclusions: Levels of anxiety and depression rose during the pandemic, particularly among economically vulnerable individuals and those experiencing economic and service disruptions. Future research should assess the effectiveness of policies targeting COVID-19 economic and service disruptions.
COVID-19 Vaccination Concerns and Reasons for Acceptance Among US Health Care Personnel
Authors: Oberleitner Lindsay M.S. , Lucia Victoria C. , Navin Mark C. , Ozdych Melissa , M. Afonso Nelia , Kennedy Richard H. , Keil Hans , Wu Lawrence , Mathew Trini A. 
Published: September 2022

Objectives: Because health care personnel (HCP) are potentially at increased risk of contracting COVID-19, high vaccination rates in this population are essential. The objective of this study was to assess vaccination status, barriers to vaccination, reasons for vaccine acceptance, and concerns about COVID-19 vaccination among HCP. Methods: We conducted an anonymous online survey at a large US health care system from April 9 through May 4, 2021, to assess COVID-19 vaccination status and endorsement of reasons for acceptance and concerns related to vaccination (based on selections from a provided list). Results: A total of 4603 HCP (12.2% response rate) completed the survey, 3947 (85.7%) had received at least 1 dose of a COVID-19 vaccine at the time of the survey, and 550 (11.9%) reported no plans to receive the vaccine. Unvaccinated HCP were 30 times more likely than vaccinated HCP to endorse religious or personal beliefs as a vaccine concern (odds ratio = 30.95; 95% CI, 21.06-45.48) and 15 times more likely to believe that personal vaccination is not needed if enough others are vaccinated (odds ratio = 14.99; 95% CI, 10.84-20.72). The more reasons endorsed for vaccination (ß = 0.60; P < .001), the higher the likelihood of having received the vaccine. However, the number of concerns about COVID-19 vaccine was not related to vaccination status (ß = 1.01; P = .64). Conclusions: Our findings suggest that reasons for vaccination acceptance and concerns about vaccination need to be considered to better understand behavioral choices related to COVID-19 vaccination among HCP, because these beliefs may affect vaccination advocacy, responses to vaccine mandates, and promotion of COVID-19 vaccine boosters.