bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer
Authors: Williams Christopher J.M. , Elliott Faye , Sapanara Nancy , Aghaei Faranak , Zhang Liping , Muranyi Andrea , Yan Dongyao , Bai Isaac , Zhao Zuo , Shires Michael , Wood Henry M. , Richman Susan D. , Hemmings Gemma , Hale Michael , Bottomley Daniel , Galvin Leanne , Cartlidge Caroline , Dance Sarah , Bacon Chris M. , Mansfield Laura , Young-Zvandasara Kathe , Sudan Ajay , Lambert Katy , Bibby Irena , Coupland Sarah E. , Montazeri Amir , Kipling Natalie , Hughes Kathryn , Cross Simon S. , Dewdney Alice , Pheasey Leanne , Leng Cathryn , Gochera Tatenda , Mangham D. Chas , Saunders Mark , Pritchard Martin , Stott Helen , Mukherjee Abhik , Ilyas Mohammad , Silverman Rafael , Hyland Georgina , Sculthorpe Declan , Thornton Kirsty , Gould Imogen , O'Callaghan Ann , Brown Nicholas , Turnbull Samantha , Shaw Lisa , Seymour Matthew T. , West Nicholas P. , Seligmann Jenny F. , Singh Shalini , Shanmugam Kandavel , Quirke Philip 
Published: June 2023

Abstract

Purpose:
High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis.

Experimental Design:
Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS).

Results:
A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56–0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50–0.86; P = 0.002]. The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection.

Conclusions:
High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice.
See related commentary by Randon and Pietrantonio, p. 4021
Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination–Deficient Leukemia Cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz 
Published: June 2023

Abstract

DNA polymerase theta (Polθ, encoded by POLQ gene) plays an essential role in Polθ-mediated end-joining (TMEJ) of DNA double-strand breaks (DSB). Inhibition of Polθ is synthetic lethal in homologous recombination (HR)-deficient tumor cells. However, DSBs can be also repaired by PARP1 and RAD52-mediated mechanisms. Because leukemia cells accumulate spontaneous DSBs, we tested if simultaneous targeting of Polθ and PARP1 or RAD52 enhance the synthetic lethal effect in HR-deficient leukemia cells. Transformation potential of the oncogenes inducing BRCA1/2-deficiency (BCR-ABL1 and AML1-ETO) was severely limited in Polq−/−;Parp1−/− and Polq−/−;Rad52−/− cells when compared with single knockouts, which was associated with accumulation of DSBs. Small-molecule inhibitor of Polθ (Polθi) when combined with PARP or RAD52 inhibitors (PARPi, RAD52i) caused accumulation of DSBs and exerted increased effect against HR-deficient leukemia and myeloproliferative neoplasm cells.

Implications:
In conclusion, we show that PARPi or RAD52i might improve therapeutic effect of Polθi against HR-deficient leukemias.
Diversity and abundance of aquatic birds in Koonthankulam village pond, Tamil Nadu, India
Authors: Selvam Muralikrishnan  , Esakkimuthu Shanmugam  , Natarajan Arun Nagendran  , Duraisamy Pandiaraja  
Published: June 2023

The diversity of birds in Koonthankulam pond, located in Koonthankulam village (8.495N, 77.755E), Tirunelveli district, southern Tamil Nadu, was studied. A total of 90 species belonging to 21 orders, 42 families, and 73 genera were recorded. The study recorded seasonal migrants such as Black Ibis, Oriental White Ibis, Bar-headed Goose & Spoonbill and indigenous species including the Pond Heron, Cattle Egret, White-breasted Kingfisher, Red-wattled Lapwing, Rose-ringed Parakeet, Purple-rumped Sunbird, Hoopoe, and Indian Robin. The primary data were analyzed by principal component analysis, cluster, and analysis of variance. Analysis of variance showed that the Menhinick index is statistically significant P <0.05. A structural equation model was applied to analyze the physico-chemical parameters of water samples collected from the sampling site. Analysis of experimental data through the structural equation model indicates temperature and dissolved oxygen may indirectly affect bird diversity.
Monitoring Extreme Floods and Droughts in the Amazon Basin with Surface-Water-Based Indices
Authors: Parrens Marie , Al-Bitar Ahmad , Santos Fleischmann Ayan 
Published: June 2023

Abstract
Extreme droughts and floods in the Amazon have great implications for ecosystems and societies. Over the last decade, the region has undergone major extreme events with no equivalent in the previous 100 years. Wetlands have been greatly impacted by these events. This study aims at presenting new indicators for wetlands based on water surface extent (WSE): duration of the flooded and nonflooded season, number of days of extreme events, delay of the start of the flooded season, and severity for each season. These indicators are more adapted for monitoring of wetlands than those based on precipitation, discharge, or groundwater information. They are computed for seven major Amazon subbasins for flooded and nonflooded seasons. These indicators improve our knowledge of the temporal behavior of the water surface during different extreme events, such as the 2015/16 drought and the 2014 flood that occurred in the Madeira basin. For the Negro basin and from the point of view of wetlands, the 2015 nonflooded season was 55% more severe than the average of the nonflooded season during the 2011–18 period. For the Paru, Trombetas, Negro, and Solimões basins, we found that a delay in the arrival of the flooded season led to a weak flood season in terms of severity. No correlation between the onset of the flooded season and its severity was found for the Madeira, Xingu, and Tapajós basins. Future hydrometeorological monitoring systems would benefit from including, in addition to variables such as river discharge and water elevation, precipitation, and vegetation dynamics, a severity index based on water surfaces as proposed in this study.
Near-Infrared Fluorescence Imaging With Indocyanine Green to Predict Clinical Outcome After Revascularization in Lower Extremity Arterial Disease
Authors: Tange Floris P. , van den Hoven Pim , van Schaik Jan , Schepers Abbey , van der Bogt Koen E.A. , van Rijswijk Catharina S. P. , Putter Hein , Vahrmeijer Alexander L. , Hamming Jaap F. , van der Vorst Joost R. 
Published: June 2023

Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group ( P-values <.001), while no significant differences were seen in the group without clinical improvement ( P-values .168–.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups ( P-values within .002–.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients.
A Critical Race Theory Assessment of Law Student Needs
Authors: Deo Meera E. 
Published: June 2023

Background/Context: Law students of color have been struggling to recover from the heightened challenges they endured during the first two years of the pandemic. Struggles with food insecurity, financial anxiety, and emotional strain contribute to declining academic success for populations that were marginalized on law school campuses long before COVID. Legislative support is necessary to support students through this era so they can maximize their full potential. Purpose/Objective/Research Question/Focus of Study: The study seeks to understand law students’ challenges during COVID and consider ways that administrators, legislators, and others can ameliorate their struggles. The objective is to provide greater support to already marginalized students during a time of significant stress and pressure. The focus of the study is on serving the needs of students of color, particularly women of color (drawing from an intersectional raceXgender framework from critical race theory). Research Design: The article draws on data from the Law School Survey of Student Engagement (LSSSE). With participation from partner law schools, LSSSE collects annual longitudinal data from law students, now housing responses from almost 300,000 students over 19 years. This study of law student needs draws from more than 13,000 responses collected in spring 2021, highlighting findings from the Coping with COVID module, a short set of questions focused on anticipated student challenges during the pandemic. The article presents findings disaggregated by race as well as raceXgender to underscore ways that COVID deepened existing disparities and heightened challenges for already vulnerable populations. Conclusions/Recommendations: The article concludes with recommendations for both institutional and legislative solutions to the identified student struggles. Law schools must allocate greater resources to student needs that range from mental health counseling to academic support—and only after first identifying the unique challenges facing women of color and other students traditionally left at the margins. Legislators must recognize that law students, while privileged in many ways, nevertheless need ongoing support to meet their basic needs; they should consider expanding Supplemental Nutrition Assistance Program (SNAP) benefits to cover law students, providing more financial aid and loan forgiveness, and prioritizing rental assistance so that law students can focus on their academic success and reach their full potential as attorneys.
Role and mechanism of leukemia inhibitory factor receptor in cervical cancer invasion and metastasis
Authors: Hu Hengfen , Zhao Qihui , Sang Yufei , Xiao Yanqing , Jiang Na 
Published: June 2023

Objective To investigate the relationships of leukemia inhibitory factor receptor (LIFR) with cervical cancer invasion and metastasis. Methods From January 2021 to December 2022, 45 patients treated for cervical cancer and lung metastases were identified. Western blotting was used to determine the expression of Hippo–YAP signaling pathway-related proteins. Meanwhile, 40 healthy Sprague-Dawley nude mice were used and evenly randomized into two groups, which were injected with LIFR-overexpressing (study group) or normal cervical cancer cells (control group). The lung tissue of nude mice was removed for hematoxylin–eosin staining, and the number of lung cell metastases in nude mice was counted. Results The highest LIFR mRNA expression was found in paracancerous tissue, followed by cervix cancer tissue and metastatic lesions. The study group exhibited higher LIFR, P-YAP, and P-TAZ protein expression and lower YAP and TAZ protein expression than the control group. The study group had a lower number of lung metastases than the control group. Conclusion Decreased expression of LIFR and decreased phosphorylation of Hippo–YAP signaling pathway-related proteins might be the underlying mechanisms that promote lung metastasis of cervical cancer.
Decreased circulating CD73 and adenosine deaminase are associated with disease severity in hospitalized patients with COVID-19
Authors: Rud Jonathan , Riker Richard R , Eldridge Ashley , Lord Christine , deKay Joanne T , May Teresa L , Gagnon David J , Sawyer Douglas , Ryzhov Sergey , Seder David B 
Published: June 2023

Objective SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity. Methods Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA. These concentrations were compared to healthy control plasma that is commercially available and was biobanked prior to the start of the pandemic. Additionally, outcomes such as WHO ordinal scale for disease severity, ICU admission, needed for invasive ventilation, hospital length of stay, and development of thrombosis during admission were used as markers of disease severity. Results Our results show that both CD73 and ADA are decreased during SARS-CoV-2 infection. The level of circulating CD73 is directly correlated to the severity of the disease defined by the need for ICU admission, invasive ventilation, and hospital length of stay. Low level of CD73 is also associated with clinical thrombosis, a severe complication of SARS-CoV-2 infection. Conclusion Our study indicates that adenosine metabolism is down-regulated in patients with COVID-19 and associated with severe infection. Further large-scale studies are warranted to investigate the role of the adenosinergic anti-inflammatory CD73/ADA axis in protection against COVID-19.
Association of Hospital Mortality With Initiation of Mechanical Ventilation on a Weekend: A Retrospective Cohort Study
Authors: Rai Karan , Douglas Ivor S. , Mehta Anuj B. 
Published: June 2023

Rationale Increased mortality in patients admitted to hospitals on weekends is a well-described phenomenon labeled the “weekend effect.” Studies evaluating the weekend effect in intensive care units (ICUs) have arrived at conflicting results. Identifying a weekend effect for critically-ill patients may inform clinical care pathways and resource allocation. Objectives Determine the association of initiation of mechanical ventilation (MV) upon admission on a weekend versus weekday with hospital mortality. Methods We conducted a retrospective cohort study of non-surgical adult patients using the California Patient Discharge Database from 2018 to 2019. We identified MV initiated on the day of admission and diagnoses using discharge billing codes. The primary exposure was admission and initiation of MV on a weekend versus weekday and the primary outcome was hospital mortality. Hierarchical logistic regression was used to determine the association between hospital mortality and MV initiation timing, adjusting for case-mix. Results Among 90 288 admissions in 2018 and 2019 meeting inclusion criteria, 24 771 (27.5%) had MV initiated on weekends, while 65 517 (72.6%) had MV initiated on weekdays. Patient demographics and comorbidities were similar between groups. Chronic alcohol and substance use disorders, and acute intoxications and traumas were more prevalent among patients with MV initiated on weekends. No difference in hospital mortality was observed with initiation of MV on weekends versus weekdays (23.1% vs 22.8%, ARD = 0.3%, aOR = 1.02, 95% CI 0.98, 1.07). Conclusions Contrary to prior studies, no increased mortality was observed among newly admitted patients initiated on MV on weekends compared to weekdays. While weekend effects may exist in other settings, newly admitted patients likely have MV initiated in the emergency department or ICU, which tend to have more consistent staffing levels. Further research is needed to determine if care patterns in these units could be used as a model for units where weekend effects continue to impact outcomes.
Long-term cause of death patterns and mode of breast cancer detection in The Netherlands, 2004−2019
Authors: Otten Johannes D M , Verbeek André L M , Broeders Mireille J M 
Published: June 2023

Objective Early detection through mammographic screening and various treatment modalities of cancer may have changed life expectancy and cause-specific mortality of breast cancer patients. We aimed to determine the long-term cause of death patterns in screening-detected patients and clinically diagnosed patients in the Netherlands compared with the general population. Methods Using data from the Netherlands Cancer Registry and Statistics Netherlands of around 26,000 women, aged 50–75 at diagnosis and surgically treated for invasive breast cancer in 2004–2008, we compared patients with screening-detected and clinically diagnosed cancer for major causes of death until 2020. The expected number of all-cause and cause-specific deaths was calculated using rates of the general population. Results During the follow-up period, 4310 women died. The age-standardised all-cause mortality ratio for the screening-detected cancer group was 1.41 (95% confidence interval (95% CI), 1.37–1.46). A higher mortality ratio was observed for patients with clinically detected cancer: 2.27 (95% CI, 2.19–2.34). The observed versus expected breast cancer mortality ratio in the screening-detected patient group was 8.92 (95% CI, 8.45–9.40) and 20.23 (19.38–21.09) in the clinical group. Excess mortality was found for lung cancer in both patient groups, and small elevations for circulatory and respiratory disease in the clinically detected group. Conclusion Our results indicate that for the screening group no other causes of death but breast and lung cancer were prominent compared with the general population. The clinical group showed excess mortality for some other causes of death as well, suggesting a less healthy group compared with the general population.
Layperson-Supported Internet-Delivered Cognitive Behavioral Therapy for Depression Among Older Adults
Authors: Xiang Xiaoling , Kayser Jay , Turner Skyla , Zheng Chuxuan 
Published: June 2023

Purpose This study explores the feasibility, acceptability, and treatment outcomes of Empower@Home, a digital cognitive behavioral therapy intervention for geriatric depression. Method Participants with depressive symptoms (PHQ-9 ≥ 5) underwent a nine-session remote intervention supported by a lay coach ( N = 103). Results Most participants (91%) completed all nine sessions (mean = 8.5). According to the Treatment Evaluation Inventory, participant attitudes toward the program were largely positive. A medium effect in depression reduction was observed following the intervention (Cohen's d = 0.75) and at a 10-week follow-up (Cohen's d = 0.60). This reduction was large (Cohen's d = 1.31 at posttest and Cohen's d = 1.18 at 10-week follow-up) among those who presented with moderate depression at baseline (PHQ-9 ≥ 10). Significant improvements were also reported in anxiety, social isolation, loneliness, and behavioral activation. Discussion Empower@Home is a promising, acceptable digital mental health intervention for treating depression in older adults.
Growth and Symmetry of the Levator Veli Palatini Muscle Within the First Two Years of Life
Authors: Kotlarek Katelyn J. , Levene Sierra , Piccorelli Annalisa V. , Allen Gregory C. , Barhaghi Krystle , Neuberger Ilana 
Published: June 2023

Objective To quantify differences in levator veli palatini (LVP) muscle dimensions based on age, sex, and race and determine the typical range of asymmetry between the left and right sides of the LVP under age 2 Design Retrospective cohort study Setting Children's tertiary care hospital Participants A retrospective chart review of non-cleft patients under 2 who received a volumetric FLAIR MRI sequence within the past 18 months identified 216 patient scans. Exclusion criteria left 200 scans for analysis. Measurements of the LVP were obtained consistent with previous literature. Interventions Corrected age, sex, and race Main Outcome Measure(s) LVP muscle dimensions Results A significant ( P < .0001) difference between corrected age groups based on the overall combination of LVP variables after controlling for sex and race. Significant age differences included average extravelar length ( P < .0001), average intravelar length ( P < .0001), midline thickness ( P < .0001), and average ( P < .0001) and difference ( P = .0413) in insertion thickness. Significant sex differences included average intravelar length ( P = .0412) and average insertion thickness ( P = .0281). Significant race differences included average insertion thickness ( P = .0334) and difference in intravelar length ( P = .0473). Differences between left and right total length ( P = .0491) and angle of origin ( P < .0001) were significant. Conclusions Differences in LVP morphology were observed in individuals under 2 years or age related to age, sex, and race. While asymmetry was significant in some dimensions, it varied by age range.