bluuebunny/crossref_metadata_2025_split huggingface dataset:
AFDN Deficiency Promotes Liver Tropism of Metastatic Colorectal Cancer
Authors: Liao Shaoxia , Deng Jingwen , Deng Mengli , Chen Chaoyi , Han Fengyan , Ye Kehong , Wu Chenxia , Pan Lvyuan , Lai Maode , Tang Zhe , Zhang Honghe 
Published: July 2024

Abstract
Liver metastasis is a major cause of morbidity and mortality in patients with colorectal cancer. A better understanding of the biological mechanisms underlying liver tropism and metastasis in colorectal cancer could help to identify improved prevention and treatment strategies. In this study, we performed genome-wide CRISPR loss-of-function screening in a mouse colorectal cancer model and identified deficiency of AFDN, a protein involved in establishing and maintaining cell–cell contacts, as a driver of liver metastasis. Elevated AFDN expression was correlated with prolonged survival in patients with colorectal cancer. AFDN-deficient colorectal cancer cells preferentially metastasized to the liver but not in the lungs. AFDN loss in colorectal cancer cells at the primary site promoted cancer cell migration and invasion by disrupting tight intercellular junctions. Additionally, CXCR4 expression was increased in AFDN-deficient colorectal cancer cells via the JAK-STAT signaling pathway, which reduced the motility of AFDN-deficient colorectal cancer cells and facilitated their colonization of the liver. Collectively, these data shed light on the mechanism by which AFDN deficiency promotes liver tropism in metastatic colorectal cancer.
Significance: A CRISPR screen reveals AFDN loss as a mediator of liver tropism in colorectal cancer metastasis by decreasing tight junctions in the primary tumor and increasing interactions between cancer cells and hepatocytes.
SJPedPanel: A Pan-Cancer Gene Panel for Childhood Malignancies to Enhance Cancer Monitoring and Early Detection
Authors: Kolekar Pandurang , Balagopal Vidya , Dong Li , Liu Yanling , Foy Scott , Tran Quang , Mulder Heather , Huskey Anna L.W. , Plyler Emily , Liang Zhikai , Ma Jingqun , Nakitandwe Joy , Gu Jiali , Namwanje Maria , Maciaszek Jamie , Payne-Turner Debbie , Mallampati Saradhi , Wang Lu , Easton John , Klco Jeffery M. , Ma Xiaotu 
Published: July 2024

Abstract

Purpose:
The purpose of the study was to design a pan-cancer gene panel for childhood malignancies and validate it using clinically characterized patient samples.

Experimental Design:
In addition to 5,275 coding exons, SJPedPanel also covers 297 introns for fusions/structural variations and 7,590 polymorphic sites for copy-number alterations. Capture uniformity and limit of detection are determined by targeted sequencing of cell lines using dilution experiment. We validate its coverage by in silico analysis of an established real-time clinical genomics (RTCG) cohort of 253 patients. We further validate its performance by targeted resequencing of 113 patient samples from the RTCG cohort. We demonstrate its power in analyzing low tumor burden specimens using morphologic remission and monitoring samples.

Results:
Among the 485 pathogenic variants reported in RTCG cohort, SJPedPanel covered 86% of variants, including 82% of 90 rearrangements responsible for fusion oncoproteins. In our targeted resequencing cohort, 91% of 389 pathogenic variants are detected. The gene panel enabled us to detect ∼95% of variants at allele fraction (AF) 0.5%, whereas the detection rate is ∼80% at AF 0.2%. The panel detected low-frequency driver alterations from morphologic leukemia remission samples and relapse-enriched alterations from monitoring samples, demonstrating its power for cancer monitoring and early detection.

Conclusions:
SJPedPanel enables the cost-effective detection of clinically relevant genetic alterations including rearrangements responsible for subtype-defining fusions by targeted sequencing of ∼0.15% of human genome for childhood malignancies. It will enhance the analysis of specimens with low tumor burdens for cancer monitoring and early detection.
Performance of Caged Broilers and Uncaged Broilers Fed with Activated Bamboo Charcoal and Bentonite Clay Mineral as Feed Additives
Authors: Cacerez Jay Mark , Gacutan Jr. Manuel , Godinez Cyrill John , Yap Karen Luz 
Published: July 2024

The issue of animal welfare and the usage of antibiotics resulted in the development of different rearing systems and the use of feed additives as antibiotic alternatives. Cage-free broiler production allows birds to express their normal behavior promoting better welfare of the animal. The study aimed to investigate the growth performance of broiler chickens reared in cages and uncaged with feed additives. A total of 180 COBB broilers were used and randomly distributed into 6 different treatments and replicates following a randomized complete block design. The birds were weighed prior to arrival, 1st week, 2nd week, 3rd week, 4th week, and 5th week to determine the growth performance parameters. Economic analysis was also measured after the end of the study. The data was analyzed using Proc Mixed of SAS v. 9.4, and group comparison was used to evaluate the differences between the control and experimental groups. The result showed significant differences in feed intake at 1st week (p=0.0249) compared to the birds reared in an uncaged system. Feed intake in subsequent weeks and other growth performance parameters showed no significant differences throughout the study. Birds fed with 0.5% activated bamboo charcoal and bentonite clay obtained a higher return on investment than in 1% inclusion. These results imply that uncaged birds have the same growth performance with caged birds and could express their natural behavior at the same time. The result also revealed that better performance and profitability can be achieved at 0.5% inclusion of feed additives in the diet.
A Sequential Explanatory: The Academic Risk-taking among Tenth Graders in Public Senior High School
Authors: Tan Andrea G. , Contreras Izzy N. , Barona Norie Jean P. , Yumul John Loyd R. , Francisco Jericho M. , Nabartey Razvan Chloe G. , Dominado Noel L. 
Published: July 2024

ABSTRACT

This sequential explanatory research aims to determine the academic risk-taking of tenth graders. The result of the study was the basis of the proposed intervention plan to improve their confidence, support, and motivation to take risks in their academics. A mixed-method sequential explanatory design was used, involving 103 tenth graders in one of the public schools in Cluster I Schools Division of Pampanga. The study revealed that fear of failure, lack of support and motivation, discouragement, judgment, and low self-esteem are why they are not taking risks in their academics. Moreover, the study discovered that this is why the participants struggle with their academic curriculum and have less interest in academics. It affects the participant's behaviour and the school's performance. Even though it is difficult to feel supported because of the environment that they have and how their relationships with the people around them actually work, the findings eventually shed light on the factors that contribute to the student's level of academic risk-taking. They need the support and motivation of their families and friends, encouragement to have high self-esteem and to be motivated to take risks without worrying about failure, and the willingness to take risks despite the difficulties that they may encounter so that they will achieve their goals of having good grades and boost their confidence to try new things beyond their capabilities. Therefore, the researchers made an intervention plan to address and improve the student's academic risk-taking behavior.
Recommendations included providing better equipment, comprehensive trainings on crisis communication, news writing and cybersecurity, fostering organizational collaboration, and recruiting specialists. Finally, a Course Instructional Guide for Public Affairs Officers was developed and proposed for adoption and implementation to hone their effectiveness in promoting the PCG’s mission and functions.
Mathematics E-learning Packets for Technical and Livelihood Education (TLE) Automotive Servicing
Authors: Tuazon Jonathan C. 
Published: July 2024

This study aimed to develop and evaluate Mathematics e-learning packets tailored for Technical and Livelihood Education (TLE) Automotive Servicing students at a public national high school, in the City Schools Division of Marikina for the School Year 2023-2024. The impetus for the study was based on the increasing number of learners who are having difficulty solving basic mathematical problems. The research addressed the following questions: (1) identifying Mathematics 9 topics suitable for e-learning packets based on literature review, (2) evaluating the developed packets by automotive and mathematics teachers according to DepEd guidelines concerning content quality, instructional quality, technical quality, assessment, visuals, and plan layout, (3) assessing any significant differences between the evaluations of the two groups of respondents, and (4) gathering comments and suggestions for improvement. Utilizing a descriptive research method, the study involved evaluations from 15 mathematics teachers and 15 automotive teachers from two public national high schools in Marikina City, Philippines. Data were analyzed using Weighted Mean and the Mann-Whitney U Test. Key findings include (1) prioritized topics under the Matatag Curriculum: perpendicular and parallel lines, relations and functions, quadratic functions and equations, direct and inverse variations, trigonometric ratios, and probability of simple events; (2) both groups rated the e-learning packets highly acceptable, with grand weighted means of 3.50 and 3.60, respectively; (3) no significant difference was found between the evaluations of the two groups; (4) respondents praised the packets' adequacy, organization, relevance, and interactivity, offering suggestions to incorporate more visuals, expand topics and activities, add video demonstrations, and involve industry professionals. In conclusion, the developed e-learning packets were well-received and deemed effective, with recommended enhancements aimed at further enriching the learning experience and bridging theoretical knowledge with practical application.
Abstract 102: Trained Immunity Impairs Inflammation Resolution And Dampens Efferocytosis
Authors: Gonzalez Azuah L , Gu Katherine , Dungan Matthew M , Wong Blenda , Fuller Kristin , Michell Danielle L , Rahman Jamshed , Spite Matthew R , Vickers Kasey C , Brown Jonathan D , Doran Amanda C 
Published: July 2024

Chronic inflammation is a major driver of atherosclerotic cardiovascular disease, and therapeutics that target inflammation reduce clinical cardiac events beyond levels seen with conventional strategies targeting cholesterol alone. Recent findings suggest innate immune cells maintain ‘memory’ of prior exposure to inflammatory stimuli, a phenomenon known as ‘trained immunity’. In response to inflammatory stimuli, macrophages undergo metabolic and epigenetic rewiring that primes them to mount an augmented response upon a second exposure. Oxidized low-density lipoproteins (oxLDL) have recently been shown to be potent triggers of trained immunity.
While trained immunity has been shown to promote inflammation, little is known about how immune training impacts efferocytosis. Therefore, we hypothesize that trained immunity in macrophages promotes inflammation by impairing efferocytosis.

We treated murine bone marrow progenitors with oxLDL for 24 hours, then washed and differentiated them into macrophages (BMDMs). Upon assessing efferocytosis, trained BMDMs were able to ingest a first apoptotic cell (AC) better than untrained BMDMs yet had an impaired ability to take up additional ACs, reflecting a defect in continual efferocytosis. Using an
in vivo
approach, we transplanted donor bone marrow from
Ldlr
-/-
mice fed a chow or Western diet into naïve C57BL/6 recipients. After recovery, we elicited peritoneal macrophages to assess efferocytosis and found that recipients receiving marrow from Western diet fed
Ldlr
-/-
mice not only displayed impaired efferocytosis, but also significantly upregulated PGE
2
production, suggesting impaired resolution. To determine whether PGE
2
is a mediator of trained immunity, we primed bone marrow progenitors with PGE
2
and differentiated them into BMDMs. We found that macrophages primed with PGE
2
elaborated higher levels of inflammatory cytokines in response to LPS stimulation than controls.

Overall, these findings demonstrate that oxLDL/Western diet-training impinges on the resolution program by impairing efferocytosis and are durable effects that demonstrate heritability. Future directions include determining the impact of these findings on the development of atherosclerosis.
Abstract 1131: Delivery Of Allogeneic Mitochondria Reverses Signatures Of Endothelial Aging & Senescence
Authors: Headley Colwyn A , Hu Caroline , Chiang Gladys , Oropeza Beu , Tsao Philip S , Huang Ngan F 
Published: July 2024

Mitochondrial dysfunction is a key factor in vascular aging, including endothelial cell (EC) dysfunction. This research investigates whether introducing mitochondria from allogeneic fibroblasts into human microvascular ECs can mitigate the cellular abnormalities associated with aging.
Mitochondria were transferred into ECs of different passages (p6-14) using centrifugation. Post mito-transfer, the metabolic activity, mitochondrial network (density), and the proliferative capacity of ECs were evaluated through extracellular flux analysis, confocal microscopy, and 5-ethynyl-2'-deoxyuridine incorporation (proliferation assay), respectively.
Results show that compared to age matched control ECs, mito-transferred ECs exhibited no change in their oxygen consumption rates linked to mitochondrial respiration. Additionally, while early passage ECs (p6-7) had no change in glycolytic activity (compared to controls), middle (p10-11) and late passage ECs (p10-14) had considerable increases in their glycolytic activity post mito-transfer. Mitochondrial network analysis additionally revealed that the mitochondrial density of early passage ECs were unaffected by mito-transfer, while late passage ECs had enhanced mitochondrial networks, including total volume, and branching post mito-transfer. Lastly, late passage ECs demonstrated a 25% increase in proliferation after mito-transfer.
These findings indicate that aging in ECs is linked to increased oxidative phosphorylation metabolism, and that mito-transfer can reduce senescence-associated oxidative glucose metabolism and enhance EC proliferation. This positions mito-transfer as a promising strategy for improve EC function in cardiovascular aging.
Abstract 155: Plasma Kallikrein Is A Key Driver Of Basal Activation Of Coagulation Under Conditions Of C1 Inhibitor Deficiency
Authors: Grover Steven P , Horvath Hanga R , Polai Zsofia , Sundler Bjorkman Linda , Bendapudi Pavan K , Mackman Nigel , Farkas Henriette 
Published: July 2024

C1 inhibitor (C1INH) functions as a key endogenous inhibitor of contact pathway coagulation factors XII, XI and plasma kallikrein (PKa). Patients with a congenital deficiency in C1INH suffer from a rare swelling disorder called hereditary angioedema (HAE) caused by excess bradykinin generation. Patients with HAE also have elevated circulating levels of markers of activation of coagulation and an increased risk of venous thromboembolism, phenotypes recapitulated in C1INH-deficient mice. We sought to evaluate the molecular mechanism by which C1INH deficiency leads to increased basal activation of coagulation and venous thrombosis.
We hypothesized that PKa serves as a key driver of activation of coagulation in humans and mice with congenital C1INH deficiency.
Patients with C1INH deficiency-associated HAE were treated with the PKa inhibitor lanadelumab with plasma samples collected before and after treatment. Plasma levels of coagulation markers and contact pathway-initiated thrombin generation were determined. C1INH-deficient mice were treated with the PKa inhibitor avoralstat, the FXIIa inhibitor garadacimab, FXII small interfering RNAs, FXI antisense oligonucleotides, the anti-tissue factor antibody 1H1 or appropriate controls and plasma coagulation markers were measured.
Treatment of HAE patients with the PKa inhibitor lanadelumab significantly reduced plasma levels of prothrombin fragment 1.2, thrombin antithrombin (TAT) complexes and D-dimer at 6 months after treatment initiation (P<0.05). Interestingly, landalumab had no significant effect on contact pathway-initiated thrombin generation. In experiments with C1INH deficient mice, TAT complexes were significantly reduced by PKa inhibition (P<0.01) but not by inhibition of FXIIa or FXIa. Interestingly, tissue factor inhibition also significantly reduced plasma TAT complexes (P<0.01). This data suggests that under conditions of C1INH deficiency PKa potentiates activation of coagulation through a non-canonical pathway involving tissue factor.
These findings demonstrate that C1INH is a physiologically relevant anticoagulant with C1INH deficiency resulting in enhanced kallikrein-mediated activation of basal coagulation.
Association between Homelessness and Temperature-Related Health Emergencies in the United States
Authors: Harris Andrea W. , Albrecht Jennifer 
Published: July 2024

Abstract
Temperature-related illness (TRI) encompasses heat-related illness, such as heat exhaustion and heatstroke, and cold-related illness, such as frostbite and hypothermia. TRI is typically the result of exposure to ambient weather conditions; because of this, unhoused individuals are hypothesized to have higher risk of TRI. However, no national epidemiological studies have been completed to determine this risk. The objective of this study was to determine the association between homelessness and emergency department (ED) diagnosis of TRI in the United States. We conducted a cross-sectional study of adult ED visits in the United States from 2005 through 2020 using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS), a nationally representative sample of nonfederal ED patient visits. Housing status (housed versus unhoused) was measured using NHAMCS patient residence category, with blank responses excluded. TRI was defined as ED clinician diagnosis of heat- or cold-related illness using International Classification of Disease, versions 9 and 10 (ICD-9 and ICD-10) codes. Multivariable logistic regression was used to determine adjusted odds of TRI by housing status. There were 323 606 nonpediatric ED visits in the NHAMCS sample. TRI diagnosis was present in 288 (0.09%) visits. 4099 visits (0.9%) were categorized as unhoused. After adjusting for sex, mental health diagnosis, and alcohol or substance use or use disorder, the odds ratio of TRI diagnosis in unhoused individuals was 4.08 (95% CI 2.09, 7.95) compared to housed individuals. We found a higher adjusted odds ratio of TRI diagnosis at an ED visit among unhoused individuals compared with housed individuals.

Significance Statement
Temperature-related health emergencies, or illnesses caused by exposure to ambient weather conditions, affect numerous Americans each year and are expected to become more common as climate change continues. We wanted to understand whether unhoused individuals are at higher risk of these health emergencies. We used a national sample of emergency department visits in the United States to study this and found out that unhoused individuals are at more than four times the risk of these illnesses than housed individuals. Our work highlights the need for prevention of homelessness, stable housing for housing insecure populations, and heating and cooling centers during weather emergencies.
Worldwide application and valuation of extracorporeal membrane oxygenation support during the COVID-19 pandemic (WAVES)
Authors: Zaaqoq Akram M , Heinsar Silver , Yoon Hwan-Jin , White Nicole , Griffee Matthew J , Suen Jacky Y , Bassi Gianluigi L , Fanning Jonathon P , Shehatta Ahmad Labib , Alexander Peta M.A. , Jacobs Jeffrey P. , Dalton Heidi J , Lorusso Roberto , Cho Sung-Min , Peek Giles J , Fraser John F ,   COVID-19 Critical Care Consortium (COVID Critical)
Published: July 2024

Objective The outcomes of COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) varied. We aim to investigate the variability concerning location and timeframe. We conducted a retrospective analysis of data from 351 institutions in 53 countries. The primary outcome was survival to hospital discharge or death up to 90 days from ECMO start. The associations between calendar time (month and year) of ECMO initiation and the primary outcome were examined by Cox regression modeling. Multivariable survival analyses were adjusted for the time of ECMO start, age, body mass index, APACHE II, SOFA, and the duration of mechanical ventilation before ECMO. Results 1060 adult COVID-19 patients enrolled in the COVID-19 Critical Care Consortium (COVID Critical) international registry and required VV-ECMO support. The study period is from January 2020 to December 2021. The median age was 51 years old, and 70% were male patients. Most patients were from Europe (39.3%) and North America (37.4%). The in-hospital mortality of the entire cohort was 47.12%. In North America and Europe, there was an increased probability of death from May 2020 through February 2021. Latin America showed a steady rate of survival until late in the study. South Asia, the Middle East, and Africa showed an increased chance of mortality around May 2020. In the Asian-Pacific region, after February 2021, there was an increased probability of death. The time of ECMO initiation and advanced patient age were associated with increased mortality. Conclusion Variability in the outcomes of COVID-19 patients on VV-ECMO existed within different regions. This variability reflects the differences in resources, policies, patient selection, management, and possibly COVID-19 virus subtypes. Our findings might help guide global response in the future by early adoption of patient selection protocols, worldwide policies, and delivery of resources.
A Comparison of Test-Retest Reliability and Practice Effects of Short Portable Mental State Questionnaire and Montreal Cognitive Assessment in Patients with Stroke
Authors: Chen Ta-Cheng , Lee Ya-Chen , Wang Yi-Ching , Hsieh Ton-Lin , Chen Mei-Hsiang 
Published: July 2024

Objective To compare the test-retest reliabilities and minimal detectable change (MDC) of the Short Portable Mental State Questionnaire (SPMSQ) and the Montreal Cognitive Assessment (MoCA) in patients with stroke. Methods 63 patients were recruited from 1 medical center. The SPMSQ and MoCA were administered twice, 2 weeks apart. Results Both measures showed high intraclass correlation coefficients (SPMSQ: 0.87; MoCA: 0.89) and acceptable MDC%s (SPMSQ: 14.8%; MoCA: 19.6%). A small correlation ( r = 0.30) was found between the absolute difference and average in each pair of assessments in the SPMSQ, which was close to the criterion of heteroscedasticity. A small practice effect was observed in the MoCA (Cohen’s d = 0.30). Conclusion The SPMSQ demonstrated smaller random measurement error and an absence of practice effect. When comparing the psychometric properties of the SPMSQ and MoCA as outcome measures for assessing cognitive function in patients with stroke, the SPMSQ appears to be a more suitable choice than the MoCA.