bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro drug testing using patient-derived ovarian cancer organoids
Authors: Chen Lin-Yu , Chou Yu-Ting , Liew Phui-Ly , Chu Ling-Hui , Wen Kuo-Chang , Lin Shiou-Fu , Weng Yu-Chun , Su Po-Hsuan , Wang Hui-Chen , Lai Hung-Cheng 
Published: April 2024

Abstract

Background Ovarian cancer is the most lethal gynecological cancer. As the primary treatment, chemotherapy has a response rate of only 60–70% in advanced stages, and even lower as a second-line treatment. Despite guideline recommendations, which drugs will be most effective remains unclear. Thus, a strategy to prioritize chemotherapy options is urgently needed. Cancer organoids have recently emerged as a method for in vitro drug testing. However, limited clinical correlations have been assessed with test results from cancer organoids, particularly in gynecological cancers. We therefore aimed to generate patient-derived organoids (PDOs) of ovarian cancer, to assess their drug sensitivities and correlations with patient clinical outcomes.
Methods PDOs were generated from fresh tumors obtained during surgical resection, which was then cultured under matrix gel and various combinations of growth factors. Morphological and molecular characterization of PDOs were assessed by phase contrast microscopy and paraffin-embedded histopathology. Expressions of PAX8, TP53, WT1, CK7, and CK20 were tested by immunohistochemical staining and compared with parental tumor tissues and the human protein atlas database. PDOs were subjected to in vitro drug testing to determine drug sensitivity using Titer-Glo® 3D Cell Viability Assay. PDO viability was measured, and area under the curve calculated, to compare responses to various compounds. Correlations were calculated between selected patients’ clinical outcomes and in vitro drug testing results.
Results We established 26 PDOs, including 15, 11, and 2 from ovarian, endometrial, and cervical cancers, respectively. The PDOs preserved the histopathological profiles of their originating tumors. In vitro drug testing of 10 ovarian cancer PDOs revealed individual differential responses to recommended drugs, and interpersonal heterogeneity in drug sensitivity, even with the same histology type. Among four patients who were platinum sensitive, resistant, or refractory, PDO drug responses correlated well with their clinical courses.
Conclusion In vitro drug testing using ovarian cancer organoids is feasible and correlates well with patient clinical responses. These results may facilitate development of precision chemotherapy and personalized screening for repurposed or new drugs.
CNVoyant: A Highly Performant and Explainable Multi-Classifier Machine Learning Approach for Determining the Clinical Significance of Copy Number Variants
Authors: Schuetz Robert J. , Ceyhan Defne , Antoniou Austin A. , Chaudhari Bimal P. , White Peter 
Published: April 2024

Abstract

The precise classification of copy number variants (CNVs) presents a significant challenge in genomic medicine, primarily due to the complex nature of CNVs and their diverse impact on genetic disorders. This complexity is compounded by the limitations of existing methods in accurately distinguishing between benign, uncertain, and pathogenic CNVs. Addressing this gap, we introduce CNVoyant, a machine learning-based multi-class framework designed to enhance the clinical significance classification of CNVs. Trained on a comprehensive dataset of 52,176 ClinVar entries across pathogenic, uncertain, and benign classifications, CNVoyant incorporates a broad spectrum of genomic features, including genome position, disease-gene annotations, dosage sensitivity, and conservation scores. Models to predict the clinical significance of copy number gains and losses were trained independently. Final models were selected after testing 29 machine learning architectures and 10,000 hyperparameter combinations each for deletions and duplications via 5-fold cross-validation. We validate the performance of the CNVoyant by leveraging a comprehensive set of 21,574 CNVs from the DECIPHER database, a highly regarded resource known for its extensive catalog of chromosomal imbalances linked to clinical outcomes. Compared to alternative approaches, CNVoyant shows marked improvements in precision-recall and ROC AUC metrics for binary pathogenic classifications while going one step further, offering multi-classification of clinical significance and corresponding SHAP explainability plots. This large-scale validation demonstrates CNVoyant’s superior accuracy and underscores its potential to aid genomic researchers and clinical geneticists in interpreting the clinical implications of real CNVs.
Incorporating tumor genomic profiling and drug screening through circulating tumor cell- derived organoids into clinical practice for the management of Gastrointestinal Cancers
Authors: Wu Wen-Chi , Hsu Chien-Fu , Chen Ming‑Huang , Chen San-Chi , Hung Yi‑Ping , Chiang Nai-Jung 
Published: April 2024

Abstract

Purpose
Precision medicine aims to revolutionize healthcare by tailoring treatment regimens. The study aimed to integrate comprehensive tumor genomic profiling (CTGP) by targeted-gene panel sequencing and drug screening by circulating tumor cell-derived organoids (CTOs) into clinical practice for the treatment of gastrointestinal (GI) cancers.
Methods
Nine patients with various GI cancers underwent CTGP and CTO drug sensitivity testing. CTGP results guided targeted therapy and immunotherapy, while CTO drug sensitivity predicted response to chemotherapy and targeted agents. The drug recommendations from two platforms were correlated with the treatment response from the suggested medications retrospectively.
Results
Five patients received therapies aligned with CTGP, including HER2-targeted treatment, immunotherapy, and BRAF/MEK dual inhibition, showing positive responses. CTO drug sensitivity predicted progression under regorafenib (low potential benefit) and good response to chemotherapy with high potential benefit. The combination of CTGP and CTO drug sensitivity may exhibit significant correlation with clinical outcomes during treatment with candidate drugs, demonstrating a sensitivity of 79% and an accuracy of 75%. This encompasses various treatment modalities such as chemotherapy, targeted therapy, and immunotherapy.
Conclusion
The present investigation elucidated the integration of CTGP and CTO drug sensitivity screening into clinical practice in a complementary manner, showcasing a significant correlation between testing results and treatment response. Additional prospective evaluation of these two testing modalities in a large cohort is warranted to confirm whether the inclusion of CTO drug sensitivity screening confers enhanced survival benefits compared to utilizing CTGP alone.
Can Inflammatory Index Parameters be an Indicator of Complexity in Perianal Fistula?
Authors: Celik Osman , Gundogan Ersin , Turk Gamze , Carkit Sedat , Ertan Tamer 
Published: April 2024

Abstract

Purpose: To investigate the relationship between preoperative inflammatory parameters and disease severity in patients operated for perianal fistula in our clinic between 2013-2021.
Methods: Patients between the ages of 16-78 who were operated on with the diagnosis of perianal fistula in Kayseri Şehir Training and Research Hospital between 2013-2021 and who were followed up afterward were included in the study by retrospective file search method without gender discrimination. Preoperative demographic data, laboratory parameters (platelet, neutrophil, lymphocyte, monocyte, leukocyte, CRP, albumin), surgical procedures, perioperative and postoperative complications, length of stay, and recurrences were noted.
Results: 134 patients with perianal fistula were included in the study. It was determined that 71.6% (n=96) were male, and the mean age was 44.6±13.8 years. Inflammatory parameters such as crp/albumin, neutrophil/lymphocyte, lymphocyte/crp, neutrophil/crp, lymphocyte/monocyte, platelet/lymphocyte were compared with tract length, tract thickness, presence of perifistular inflammation and presence of abscess as criteria for complex fistula formation and cut of values were created. Among these scoring values, crp/albumin, lymphocyte/crp, and neutrophil/crp ratios were statistically significant in predicting the tract characteristics defined for high recurrence and complex fistula.
Conclusion: Inflammation-based scores such as crp/albumin, lymphocyte/crp, and neutrophil/crp ratios can differentiate complex fistula from simple fistula.
The Uganda Housing Modification Study – Association between housing characteristics and malaria burden in a moderate to high transmission setting in Uganda
Authors: Nankabirwa Joaniter I , Gonahasa Samuel , Katureebe Agaba , Mutungi Peter , Nassali Martha , Kamya Moses R , Westercamp Nelli 
Published: April 2024

Abstract

Background: Scale up of proven malaria control interventions has not been sufficient to control malaria in Uganda, emphasizing the need to explore innovative new approaches. Improved housing is one such promising strategy. We describe housing characteristics and their association with malaria burden in a moderate to high transmission setting in Uganda.
Methods: Between October and November 2021, a household survey was conducted in 1500 randomly selected households in Jinja and Luuka districts. Information on demographics, housing characteristics, use of malaria prevention measures, and proxy indicators of wealth were collected for each household. A finger-prick blood sample was obtained for thick blood smears for malaria from all children aged 6 months to 14 years in the surveyed households. Febrile children had a malaria rapid diagnostics test (RDT) done; positive cases were managed according to national treatment guidelines. Hemoglobin was assessed in children aged <5 years. Households were stratified as having modern houses (defined as having finished materials for roofs, walls, and floors and closed eaves) or traditional houses (those not meeting the definition of modern house). Associations between malaria burden and house type were estimated using mixed effects models and adjusted for age, wealth, and bednet use.
Results: Most (65.5%) of the households surveyed lived in traditional houses. Most of the houses had closed eaves (85.5%), however, the use of other protective features like window/vent screens and installed ceilings was limited (0.4% had screened windows, 2.8% had screened air vents, and 5.2% had ceiling). Overall, 3,443 children were included in the clinical survey, of which 31.4% had a positive smear. RDT test positivity rate was 56.6% among children with fever. Participants living in modern houses had a significantly lower parasite prevalence by microscopy (adjusted prevalence ratio [aPR=0.80]; 95% confidence interval [CI] 0.71 – 0.90), RDT test positivity rate (aPR=0.90, 95%CI 0.81 – 0.99), and anemia (aPR=0.80, 95%CI 0.65 – 0.97) compared to those in traditional houses.
Conclusion: Our study found that even after adjusting for wealth, higher quality housing had a moderate protective effect against malaria, on top of the protection already afforded by recently distributed nets.
Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders
Authors: Mishra Himanshu K. , Wei Heather , LeRoux Melissa , Ko Insu , Rohr Kayla E. , Nievergelt Caroline M , Maihofer Adam X , Shilling Paul , Alda Martin , Berrettini Wade H , Calabrese Joseph R. , Coryell William H. , Frye Mark , Gershon Elliot , McInnis Melvin G. , Nurnberger John , Oedegaard Ketil J. , Zandi Peter P. , Kelsoe John R. , McCarthy Michael J. 
Published: April 2024

Abstract

Bipolar disorder (BD) is characterized by disrupted circadian rhythms and neuronal loss. Lithium is neuroprotective and used to treat BD, but outcomes are variable. Past research identified that circadian rhythms in BD patient neurons are associated with lithium response (Li-R) or non-response (Li-NR). However, the underlying cellular mechanisms remain unknown. To study interactions among circadian clock genes and cell survival, and their role in BD and predicting lithium response, we tested selected genes (PER1, BMAL1 and REV-ERBα) and small molecule modulators of ROR/REV-ERB nuclear receptors in models of cell survival using mouse neurons and stem-cell derived neuronal progenitor cells (NPC) from BD patients and controls. In apoptosis assays using staurosporine (STS), lithium was neuroprotective. Knockdown of PER1, BMAL1 and REV-ERBα modified cell survival across models. In NPCs, reduced expression of PER1 and BMAL1 led to more extensive cell death in Li-NR vs. Li-R. Reduced REV-ERBα expression caused more extensive cell death in BD vs. control NPCs, without distinguishing Li-R and Li-NR. In IMHN, The REV-ERB agonist GSK4112 had strong effects on circadian rhythm amplitude, and was neuroprotective in mouse neurons and control NPCs, but not in BD NPCs. Expression of cell survival genes following STS and GSK4112 treatments revealed BD-associated, and Li-R associated differences in expression profiles. We conclude that the neuroprotective response to lithium is similar in NPCs from Li-R and Li-NR. However, knockdown of circadian clock genes or stimulation of REV-ERBs reveal distinct contributions to cell death in BD patient NPCs, some of which distinguish Li-R and Li-NR.
Empower LlaMa 2 for Advanced Logical Reasoning in Natural Language Understanding
Authors: Watanabe Natsumi , Kinasaka Kudoro , Nakamura Akira 
Published: April 2024

Abstract

Enhancing LlaMa 2 through the integration of a rule-based reasoning layer and a logic inference engine, collectively referred to as LlaMa+, has markedly improved its capabilities in natural language understanding. The performance enhancements were rigorously evaluated using the sophisticated MMLU and LegalBench benchmark datasets, where LlaMa+ showed significant increases in precision, accuracy, recall, and F1-score. These improvements are indicative of the model's advanced ability to interpret and reason with complex texts, reflecting a substantial progression towards AI systems that can engage with human language in a contextually aware and cognitively profound manner. This research not only underscores the enhanced analytical abilities of LlaMa+ but also explores the implications for practical applications in fields requiring nuanced language comprehension such as legal analysis, academic research, and technical problem-solving. Future directions involve optimizing the computational efficiency of these enhancements to ensure wider applicability and exploring autonomous methods for updating the reasoning mechanisms to keep pace with evolving data and applications.
Data Encryption and Decryption Using image Steganography
Authors: Singh Aniket , Zaidi Abbas Raza , Bagh Ranjan Das 
Published: April 2024

Abstract

In today’s digital landscape, safeguarding sensitive information is of utmost importance. This research paper delves into the fusion of data encryption and decryption methodologies with image steganography, aiming to fortify the security of digital data exchange. The integration of the least significant bit (LSB) algorithm facilitates the seamless embedding of encrypted data into images, ensuring concealment from unauthorized access while preserving data integrity. Implemented as a web-based platform utilizing HTML, CSS, JavaScript, Python, and Django frameworks, the system empowers users with intuitive functionalities for image steganography, encryption, and decryption, fostering a user-friendly and secure data transmission environment.
In today’s digital era, securing sensitive data has become a paramount concern. This research paper delves into the intricate synergy between image steganography and data encryption/decryption techniques to bolster the resilience of data transfer across web infrastructures. The investigation entails the creation of a user-accessible web interface utilizing HTML, CSS, JavaScript, Python, and Django frameworks, facilitating three pivotal utilities: image steganography, encryption, and decryption. By melding these methodologies, confidential information is covertly embedded within images, fortified with encryption to thwart unauthorized access, and seamlessly decrypted for authorized parties, thereby erecting a formidable bastion of confidentiality and integrity in digital data exchanges. This paper not only presents the theoretical underpinnings but also provides practical insights into the implementation of these techniques within a web environment, thereby contributing to the advancement of secure data communication paradigms in the digital era.
Out-group/in-group personal moral dilemmas in the Kogi worldview
Authors: Cáceres Rafael Gonzalo Angarita , Serrano Jorge Francisco Maldonado 
Published: April 2024

Abstract

This research report studies how Kogi people (a small-scale society located in Northern Colombia, South America) answer personal moral dilemmas (PMD), specifically a cultural adaptation of the Footbridge scenario when the characters in the stories are in-group or out-group. Four moral scenarios were designed in which the indigenous had to judge the possibility of saving either one person or five (1 in-group or 5 out-group; 1 out-group or 5 in-group; 1 and 5 in-group, and 1 and 5 out-group). The main findings were: the participants opted for choices closer to the consequentialist than to the deontological option, and that the group bias allowed them to go from a consequentialist option to a deontological one. Our research suggests that moral judgment in the resolution of personal moral dilemmas is not unitary even within the same human group; it also suggests that moral judgment depends on two contextual factors: the group membership and the social relationship of the experiment’s subjects with the characters of the story.
Smart Assistive Stick for Visually Impaired People using YOLOv8 Algorithm
Authors: Deotale Nilesh , Raut Shubham , Patil Nirmit , Patil Vedashree , Bari Priyal 
Published: April 2024

Abstract

Technologies are constantly evolving, allowing people to live healthier and more convenient lifestyles. Sightless persons are unable to go about their daily lives, such as strolling down the street, meeting friends or family, or performing other routine jobs. In a world of ever-evolving technology, the " Smart Assistive Stick for Visually Impaired People using YOLOv8 Algorithm" represents a remarkable fusion of innovation and compassion. Yolov8 has become one of the most popular object detection models in the deep learning community. Its versatility and real-time capabilities open up new possibilities for computer vision applications
Antioxidant Potential of Calophyllum canum P. F. Stevens: Xanthones, Phenolics, and Radical Scavenging Activity
Authors: Lizazman Mas Atikah , Mian Vivien Jong Yi 
Published: April 2024

Abstract

The isolation and purification of the ethyl acetate of C. canum stem bark have yielded a new α,β-unsaturated δ-lactone compound, canumolactone (8), along with known xanthones, 1-hydroxy-7-methoxyxanthone (1), caloxanthone C (2), trapezifolixanthone (3), ananixanthone (4), euxanthone (5), gentisin (6), 2-hydroxyxanthone (7), and α-mangostin (9). In this study on C. canum extracts, the total phenolic content (TPC), total flavonoid content (TFC), and radical scavenging activity (RSA) were investigated to assess the antioxidant potential. The extraction of C. canum stem bark yielded various crude extracts, with the ethyl acetate extract showing the highest RSA (97.14 ± 0.24 %) and TPC (277.33 ± 9.65 mg GAE/g extract). The TFC values varied across extracts, with the dichloromethane extract displaying the highest TFC (117.96 ± 3.35 mg QE/g extract). A strong positive correlation was observed between TPC and RSA, indicating the significant role of phenolic compounds in the antioxidant activity of the extracts. Conversely, the relationship between TFC and RSA was weak, suggesting a minor contribution of flavonoids to the antioxidant potential of the extracts. These findings highlight the importance of phenolic compounds in determining the antioxidant activity of C. canum extracts.
Implementation of a Strengths-Based Nursing Intervention for Supporting Families in Acute Care Settings: Perspectives of Family Members and Nurses
Authors: Kiwanuka Frank , Kopra Juho , Nanyonga Rose Clarke , Sak-Dankosky Natalia , Kvist Tarja 
Published: April 2024

Abstract

Aim
To evaluate changes in family members´ perceived support and family nursing practice following the implementation of a nurse-led family strengths-based intervention in adult intensive care units.
Design
This was an implementation study that utilised a single-group pre-post-test quasi-experimental design.
Methods
The intervention involved three elements: assessment of family strengths, development of family strengths, and feedback. To support the delivery of the intervention, the intervention and supporting information was manualized. The Icelandic Family Perceived Support Scale and the Family Nursing Practice Scale were administered to family members (n = 34) and nurses (n = 30) respectively. Study outcomes were measured at baseline (TO) and immediately after the intervention (T1). Data were analysed using descriptive statistics and a repeated measures-MANOVA.
Results
family members´ perspectives on family support (emotional and cognitive support) improved after implementing the intervention. Improvements were also observed in nurses´ practice skills appraisal scores but not in nurse-family relationship scores.
Conclusion
The nurse-led family intervention implemented in intensive care settings can be a valuable tool for supporting families and nurses´ skills of working with families during the trajectory of care. Further research is needed to explore the intervention´s comparative effectiveness in diverse contexts using larger samples and randomized controlled trials with longer follow-up periods.
Impact:
Family strengths can be leveraged when designing approaches aimed at providing emotional and cognitive support to family members during the trajectory of care in acute care settings. The intervention framework based on Strengths-Based Nursing is an insightful way to facilitate nurse-family interaction and a way to enhance nurses´ practice skills of working with families.
Patient or Public Contribution:
The elements of the intervention tested in this study were directly informed by the experiences of patients´ family members. Patients´ family members were also consulted during the design stage of the intervention.
Assessment of the carbon neutral capacity of ecological slopes: A case study of wet-spraying vegetation concrete ecological river revetment
Authors: Luo Yujie , Xu Weisheng , Xu Qing , Chen Buqing , Shi Hongcai , Ye Jianjun 
Published: April 2024

ABSTRACT

This study evaluates the carbon neutrality of eco-slope protection projects to understand their role in climate change mitigation. Utilizing life cycle assessment, it defines system boundaries and compiles inventories to calculate and analyze carbon emissions and assimilations of a wet-spraying vegetation concrete eco-slope protection project in China, simplifying previous methodologies and emphasizing the critical role of vegetation. Findings indicate lifecycle carbon emissions total 608.01 tCO2e, broken down by source as follows: material (54.69%), maintenance (40.11%), energy (3.27%), transport (1.32%), and workforce (0.6%). Slope protection plants are estimated to assimilate 2,676.30 tCO2. The project is estimated to reach carbon neutrality in its 4.59th year, with an anticipated net carbon sink contribution of 2,068.29 tons over its lifespan. These results underscore eco-slope protection projects’ significant carbon neutral capacity, highlighting their importance in combating climate change and fostering the civil engineering industry's green transformation.