bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating spatial confounding by explicitly correlating Gaussian random fields
Authors: Marques Isa , Kneib Thomas , Klein Nadja 
Published: April 2022

AbstractSpatial models are used in a variety of research areas, such as environmental sciences, epidemiology, or physics. A common phenomenon in such spatial regression models is spatial confounding. This phenomenon is observed when spatially indexed covariates modeling the mean of the response are correlated with a spatial random effect included in the model, for example, as a proxy of unobserved spatial confounders. As a result, estimates for regression coefficients of the covariates can be severely biased and interpretation of these is no longer valid. Recent literature has shown that typical solutions for reducing spatial confounding can lead to misleading and counterintuitive results. In this article, we develop a computationally efficient spatial model that explicitly correlates a Gaussian random field for the covariate of interest with the Gaussian random field in the main model equation and integrates novel prior structures to reduce spatial confounding. Starting from the univariate case, we extend our prior structure also to the case of multiple spatially confounded covariates. In simulation studies, we show that our novel model flexibly detects and reduces spatial confounding in spatial datasets, and it performs better than typically used methods such as restricted spatial regression. These results are promising for any applied researcher who wishes to interpret covariate effects in spatial regression models. As a real data illustration, we study the effect of elevation and temperature on the mean of monthly precipitation in Germany.
Noncredit Career and Technical Community College Programs as a Bridge to Employers: Report on NYC Region Study
Authors: Haviland Sara , Robbins Steve , Kirova Dessi , Bochenek Jennifer , Fishtein Dan 
Published: April 2022

Noncredit community college programs provide an important route for workforce development. They offer affordable and accessible short‐term training options for individuals seeking access to middle‐skills jobs. Absent the burdens of accreditation standards, they can respond nimbly to local labor market needs. However, they can also be varied and confusing, and despite the high volume of students that they serve, they are an underexamined area in higher education. This study examines noncredit programs in the New York City labor market to determine how schools align noncredit offerings to the labor market, focusing on credential design, competencies, and market processes. It pursues a push–pull design through a combination of document review and interviews with school leaders and employers and introduces quality taxonomy for understanding employer engagement in individual programs. Implications for students, programs, schools, and employers are explored.The executive summary for this report can be downloaded at
https://www.ets.org/Media/Research/pdf/Executive_Summary_RR‐22‐09.pdf
Milk composition, traditional processing, marketing, and consumption among smallholder dairy farmers in selected towns of Jimma Zone, Oromia Regional State, Ethiopia
Authors: Duguma Belay 
Published: April 2022

AbstractIn Ethiopia, dairy products remain the most important animal source of foods including in the current study area. However, poor milk quality is frequently told constraint, and this affects smallholder dairy development. This study aimed to assess raw cow milk composition, processing, consumption, and marketing among smallholder dairy producers in selected towns of Jimma Zone, Ethiopia. Primary data were collected by surveying 52 randomly selected dairy cattle keeping households using a structured questionnaire and analysis of raw milk chemical composition. The results revealed that the average milk production was 5.98 ± 1.01 liters/household/day, of which the majority (62.9%) was marketed. About 22.7% of households reported processing milk into butter, cottage cheese, ghee, and fermented milk at household level mainly for domestic use. A combination of fresh whole milk, fermented milk, butter, cottage cheese, and ghee (51.7%) were the main dairy products consumed by respondents. About 72.2% and 6.1% of households consumed boiled and raw milk, respectively, while 100% respondents reported consuming raw fermented whole milk. Milk was channeled to consumers and retailers through informal marketing system (100%). The awareness of respondents about zoonotic diseases was found to be very low. The mean fat, lactose, and protein content of raw cow milk were significantly (p < .05) affected by breed. It is recommended that consumption of raw milk and fermented milk could pose a public health risk to consumers, implying the need for urgent farmers’ awareness creation to boil milk before consumption for prevention and control of zoonotic diseases.
Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States
Authors: Ahn Joseph C. , Lauzon Marie , Luu Michael , Noureddin Mazen , Ayoub Walid , Kuo Alexander , Sundaram Vinay , Kosari Kambiz , Nissen Nicholas , Gong Jun , Hendifar Andrew , Roberts Lewis R. , Abou‐Alfa Ghassan K. , Singal Amit G. , Yang Ju Dong 
Published: April 2022

Abstract

Background and Aims
Immunotherapy has emerged as an effective treatment for patients with advanced‐stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy.

Approach and Results
We used the US National Cancer Database to identify patients with tumor‐node‐metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first‐line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65–0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46–0.83) and Black patients (aOR: 0.71, 95% CI: 0.54–0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race‐ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004).

Conclusions
Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial‐ethnic disparities in the management of advanced HCC is urgently needed.
Proteomics‐based identification of the role of osteosarcoma amplified‐9 in hepatocellular carcinoma recurrence
Authors: Wei Xuyong , Yang Mengfan , Pan Binhua , Zhang Xiaobing , Lin Hanchao , Li Wangyao , Shu Wenzhi , Wang Kun , Khan Abdul Rehman , Zhang Xuanyu , Cen Beini , Xu Xiao 
Published: April 2022

Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies; its recurrence is associated with high mortality and poor recurrence‐free survival and is affected by multisystem and multilevel pathological changes. To identify the key proteins associated with tumor recurrence and the underlying mechanisms, proteomic profiling of tumor specimens from early recurrence and nonrecurrence patients was performed in this study. Proteomics was applied to identify differentially expressed proteins during the early recurrence of HCC after surgery. Osteosarcoma amplified‐9 (OS‐9) was discovered, and the correlation between OS‐9 expression and the clinicopathological characteristics of patients was analyzed. Invasion and migration were examined in SMMC‐7721 cells with and without OS‐9 overexpression. Proteomics was performed once again using SMMC‐7721 cells with OS‐9 overexpression to further analyze the proteins with altered expression. OS‐9 was overexpressed in the early recurrence group, and OS‐9 overexpression was associated with high serum alpha‐fetoprotein levels and poor recurrence‐free survival in 196 patients with HCC. The invasion and migration abilities of SMMC‐7721 cells were enhanced in the OS‐9 overexpression group. Bioinformatic functional enrichment methods, including Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis, revealed that the hypoxia‐inducible factor 1 (HIF‐1) and tumor necrosis factor (TNF) signaling pathways were activated in the OS‐9 overexpression group. The migration and invasion capacities of OS‐9 overexpressed HCC cell line were weakened while treated with HIF‐1α or TNF‐α inhibitors. Conclusion: Our results suggest that the overexpression of OS‐9 is related to HCC recurrence, thereby contributing to the migration and invasion capacities of HCC cell line by regulating the HIF‐1 and TNF pathways.
Ecosystem services at risk in Italy from coastal inundation under extreme sea level scenarios up to 2050: A spatially resolved approach supporting climate change adaptation
Authors: Furlan Elisa , Derepasko Diana , Torresan Silvia , Pham Hung V. , Fogarin Stefano , Critto Andrea 
Published: April 2022

Abstract
According to the latest projections of the Intergovernmental Panel on Climate Change, at the end of the century, coastal zones and low-lying ecosystems will be increasingly threatened by rising global mean sea levels. In order to support integrated coastal zone management and advance the basic “source–pathway–receptor–consequence” approach focused on traditional receptors (e.g., population, infrastructure, and economy), a novel risk framework is proposed able to evaluate potential risks of loss or degradation of ecosystem services (ESs) due to projected extreme sea level scenarios in the Italian coast. Three risk scenarios for the reference period (1969–2010) and future time frame up to 2050 under RCP4.5 and RCP8.5 are developed by integrating extreme water-level projections related to changing climate conditions, with vulnerability information about the topography, distance from coastlines, and presence of artificial protections. A risk assessment is then performed considering the potential effects of the spatial-temporal variability of inundations and land use on the supply level and spatial distribution of ESs. The results of the analysis are summarized into a spatially explicit risk index, useful to rank coastal areas more prone to ESs losses or degradation due to coastal inundation at the national scale. Overall, the Northern Adriatic coast is scored at high risk of ESs loss or degradation in the future scenario. Other small coastal strips with medium risk scores are the Eastern Puglia coast, Western Sardinia, and Tuscany's coast. The ESs Coastal Risk Index provides an easy-to-understand screening assessment that could support the prioritization of areas for coastal adaptation at the national scale. Moreover, this index allows the direct evaluation of the public value of ecosystems and supports more effective territorial planning and environmental management decisions. In particular, it could support the mainstreaming of ecosystem-based approaches (e.g., ecological engineering and green infrastructures) to mitigate the risks of climate change and extreme events while protecting ecosystems and biodiversity. Integr Environ Assess Manag 2022;18:1564–1577. © 2021 SETAC
KEY POINTS
The loss of coastal ecosystem services to extreme sea level scenarios is evaluated. The index integrates climatic, physical, and environmental indicators. About 8% of the Italian shoreline is subjected to potential ecosystem services loss. Ecosystem services at greatest risk are mainly located on the North Adriatic coast. Results can inform ecosystem-based coastal zone management and climate adaptation.
Higher genetically predicted low‐density lipoprotein levels increase the renal cancer risk independent of triglycerides and high‐density lipoprotein levels: A Mendelian randomization study
Authors: Ma Yucheng , Jian Zhongyu , Xiang Liyuan , Jin Xi 
Published: April 2022

AbstractThe causation between lipids and renal cancer remains inconclusive. Our purpose is to explore the causal relationships between the three primary lipid metabolism‐related substances, namely triglycerides (TG), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) with the risk of renal cancer using Mendelian randomization (MR) methods. Genetic instruments for lipids were acquired from the UK Biobank. Outcome data were from the FinnGen study (1397 renal cancer cases and 204 070). Single‐variable MR (SVMR) and multi‐variable MR (MVMR) analyses were conducted with TwoSampleMR package based on R 4.0.3. The random‐effect inverse‐variance weighted (IVW), MR‐Egger, weighted‐median method, and weighted mode were the four main computing methods. We found that per 1 SD elevated LDL level was causally associated with renal cancer occurrence based on SVMR (OR, 1.31, 95% CI: 1.05‐1.64, P = .016). Similar significant associations were found in other methods. However, the results of SVMR did not support significant associations between TG, and HDL with renal cancer risk in all methods. The association between LDL and renal cancer was still significant in MVMR analysis (OR for IVW method: 1.22 per 1 SD higher trait (SD, 95% CI: 1.11‐1.34, P < .001; OR for MR‐Egger: 1.22 per 1 SD higher trait, 95% CI: 1.01‐1.47, P = .042) when taking TG and HDL into consideration. Our study supported that elevated serum LDL levels is causally associated with an increased risk of renal cancer independent of TG and HDL.
Gut microbiota correlates with antitumor activity in patients with mCRC and NSCLC treated with cetuximab plus avelumab
Authors: Martini Giulia , Ciardiello Davide , Dallio Marcello , Famiglietti Vincenzo , Esposito Lucia , Corte Carminia Maria Della , Napolitano Stefania , Fasano Morena , Gravina Antonietta Gerarda , Romano Marco , Loguercio Carmelina , Federico Alessandro , Maiello Evaristo , Tuccillo Concetta , Morgillo Floriana , Troiani Teresa , Di Maio Massimo , Martinelli Erika , Ciardiello Fortunato 
Published: April 2022

AbstractGut microbiota is involved in immune modulation and immune checkpoint inhibitors (ICIs) efficacy. Single‐arm phase II CAVE‐mCRC and CAVE‐LUNG clinical trials investigated cetuximab + avelumab combination in RAS wild‐type (WT) metastatic colorectal cancer (mCRC) and chemo‐refractory nonsmall cell lung cancer (NSCLC) patients, respectively. A comprehensive gut microbiota genetic analysis was done in basal fecal samples of 14 patients from CAVE‐mCRC trial with circulating tumor DNA (ctDNA) RAS/BRAF WT and microsatellite stable (MSS) disease. Results were validated in a cohort of 10 patients from CAVE‐Lung trial. 16S rRNA sequencing revealed 23 027 bacteria species in basal fecal samples of 14 patients from CAVE‐mCRC trial. In five long‐term responding patients (progression‐free survival [PFS], 9‐24 months) significant increases in two butyrate‐producing bacteria, Agathobacter M104/1 (P = .018) and Blautia SR1/5 (P = .023) were found compared to nine patients with shorter PFS (2‐6 months). A significantly better PFS was also observed according to the presence or absence of these species in basal fecal samples. For Agathobacter M104/1, median PFS (mPFS) was 13.5 months (95% confidence interval [CI], 6.5‐20.5 months) vs 4.6 months (95% CI, 1.8‐7.4 months); P = .006. For Blautia SR1/5, mPFS was 5.9 months (95% CI, 2.2‐9.7 months) vs 3.6 months (95% CI, 3.3‐4.0 months); P = .021. Similarly, in CAVE‐Lung validation cohort, Agathobacter M104/1 and Blautia SR1/5 expression were associated with PFS according to their presence or absence in basal fecal samples. Agathobacter and Blautia species could be potential biomarkers of outcome in mCRC, and NSCLC patients treated with cetuximab + avelumab. These findings deserve further investigation.
Healthy lifestyle index and the risk of ductal carcinoma in situ of the breast in the Women's Health Initiative
Authors: Peila Rita , Lane Dorothy S. , Shadyab Aladdin H. , Saquib Nazmus , Strickler Howard D. , Manson JoAnn E. , Pan Kathy , Rohan Thomas E. 
Published: April 2022

AbstractA relatively high healthy lifestyle index (HLI) score, representing a healthy diet, participation in moderate to vigorous physical exercise, no smoking, low to no alcohol intake and a normal body mass index, has been associated with a reduced risk of invasive breast cancer. However, no study has shown an association between the HLI and the risk of ductal carcinoma in situ of the breast (DCIS), which is considered to be a nonobligate precursor of invasive breast cancer. We evaluated this association in a prospective cohort of 132 230 postmenopausal women, aged 50 to 79 years, recruited between 1993 and 1998 across the United States and enrolled in the Women's Health Initiative study. The HLI score was created and categorized into quartiles. During an average follow‐up of 15.4 years, 2035 DCIS cases were ascertained. Multivariable‐adjusted Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of HLI with the risk of DCIS. Women in the highest HLI quartile had a lower DCIS risk than those in the lowest quartile (HR4thQT = 0.80, 95% CI, 0.70‐0.92) and this association was stronger in women with a family history of breast cancer (HR4thQT = 0.70, 95% CI, 0.52‐0.93), and for ER+/PR+ DCIS (HR4thQT = 0.66, 95% CI, 0.52‐0.83). These findings suggest that there is an inverse association between HLI and risk of DCIS, and suggest that the adoption of a healthy lifestyle might lower the risk of DCIS.
Direct retrieval bias for general and specific memories for negatively valenced cues in major depression
Authors: Hallford David John , Matsumoto Noboru 
Published: April 2022

Major depressive disorder (MDD) is associated with reduced specificity in autobiographical memory. It has been argued that this tendency occurs through a failure of effortful generative retrieval, regardless of valence of cue word. However, we propose that in MDD general memories are likely to be recalled via direct retrieval, and direct retrieval is more likely for negatively valenced cues. To provide a preliminary test of this, a large sample with MDD (N = 298; M age = 47.2) completed the autobiographical memory test and indicated whether retrievals were generative or direct. Categoric and extended memories for negatively valenced cues were more often directly retrieved than generatively retrieved, and more often than direct retrieval for positively valenced cues. In contrast, categoric and extended memories for positively valenced cues were more often generatively retrieved relative to generative retrieval for negatively valenced cues. Relative to non‐clinical samples, direct retrieval for negatively valenced cues was high. Retrieval method and valence may be moderating processes in the type of memories recalled. This preliminary work presents the possibility of an extension of theory on retrieval tendencies in MDD.
Identification of the optimal primary care clinical pharmacy comprehensive medication management practice in the veterans health administration
Authors: McFarland M. Shawn , Ourth Heather , Seckel Ellina , Gould Kyleigh , Ragan Addison , Morreale Anthony 
Published: April 2022

AbstractClinical pharmacists are well‐positioned as the medication experts on the health care team to work collaboratively with providers and patients to achieve optimal medication use in order to maximize patient benefit and outcome. Comprehensive medication management (CMM) is defined as a patient‐centered approach to optimizing medication use and improving patient health outcomes that is delivered by a clinical pharmacist working in collaboration with the patient and other health care providers. Lack of fidelity in practice model design and implementation make generalization of results of clinical pharmacy CMM practice difficult. There is currently no organization that evaluates standardized implementation of clinical pharmacists providing CMM in a Patient‐Centered Medical Home (PCMH) leading to wide variability of CMM implementation within the PCMH model. The Veterans Health Administration (VA) is the largest integrated health care system in the United States. Clinical pharmacy specialists (CPS) in the VA work autonomously but collaboratively under a practice area‐based scope of practice with prescriptive authority. The goal of the Clinical Pharmacy Practice Office Platinum Practice Designation was to develop a standardized review process to recognize sites that have achieved core elements of desired primary care pharmacy practice. In this paper, we describe the creation and implementation of this process. The submission process consisted of three rounds ranging from survey, data submission, data review and validation, and a facility interview. A total of 19 submissions were completed with two sites identified as achieving greater than 90% fidelity to the CMM model and were considered best practices. The creation of a rigorous set of implementation tools and measurement metrics creates the necessary fidelity to evaluate programs across different geographic areas. Identified sites provide examples for other facilities to emulate and creates momentum for pharmacy practice advancement throughout the nation.
Evaluating an interactive teaching approach with personal genotyping to provide pharmacy students with a knowledge base for clinical pharmacogenetics
Authors: Arwood Meghan J. , McDonough Caitrin W. , Cavallari Larisa H. , Elsey Amanda R. , Frye Reginald F. , Gong Yan , Langaee Taimour , Johnson Julie A. , Wiisanen Kristin 
Published: April 2022

AbstractIntroductionAlthough the majority of pharmacy schools are teaching pharmacogenetics in their curricula, there is limited coverage of important clinical concepts and pharmacists report low comfortability in utilizing pharmacogenetic results.ObjectivesTo compare the effectiveness of a combined didactic and patient case‐based, interactive teaching approach (including optional personal genotyping) with a traditional didactic teaching strategy on students' knowledge and confidence in their ability to use pharmacogenetic data in clinical decision‐making.MethodsThe University of Florida College of Pharmacy offered elective and required courses in personalized medicine from 2014 to 2016. The elective course, Clinical Applications of Personalized Medicine, emphasized interactive patient case‐based teaching and incorporated personal genotype results into learning activities, while the required course, Personalized Medicine, primarily used a didactic lecture‐based format. Students enrolled in both courses concurrently (intervention group) and the required course alone (control group) completed pre‐ and post‐course surveys with patient case‐based assessments to evaluate their knowledge and confidence in their ability to apply genotype data to drug therapy recommendations.ResultsFifty‐two students (intervention: n = 21; control: n = 31) completed both surveys. Between the intervention and control groups respectively, there were no differences in mean pre‐course knowledge (43.1% vs 37.7% questions correct, P = .15) or median confidence scores (35 vs 40, P = .84). Mean post‐course knowledge (65.4% vs 46.9% questions correct, P < .001) and median confidence scores (97 vs 81, P = .0003) were significantly higher in the intervention vs control group, respectively. There was no correlation between students' knowledge and confidence for pre‐course assessment in either group. For the post‐course assessment, knowledge and confidence were positively correlated in the intervention group (adjusted r = .46, adjusted P = .04), but were not correlated in controls.ConclusionOur data suggest that a combined teaching strategy that employs didactic lecture plus patient‐centered, case‐based teaching and personal genotype application improves students' ability to accurately self‐assess their knowledge in pharmacogenetics.