bluuebunny/crossref_metadata_2025_split huggingface dataset:
The policy formulation process, and the role of actors in the policy formulation and implementation process: A policy analysis of the Kenyan free maternity policy
Authors: Oyugi Boniface , Audi-Poquillon Zilper , Kendall Sally , Peckham Stephen , Barasa Edwine 
Published: January 2024

AbstractKenya is one of the many African countries committed to advancing its health system reforms by providing affordable and equitable access to essential health services. In 2016, the Government of Kenya unveiled an expanded free maternity care policy called‘Linda Mama’to provide essential health services for pregnant women. We explored the agenda setting and the formulation of this policy to understand the processes, content and context, and the role of the actors in the formulation and implementation. We conducted an exploratory qualitative study, which involved document review, key informant interviews (KIIs) with national stakeholders, and in-depth interviews with County officials and health care workers (HCWS). We used a theoretical framework capturing the preliminary situation analysis of the policy, the processes, the content, and the stakeholders’ roles in the formulation and implementation. This study was conducted in three facilities (levels 3, 4, and 5) in Kiambu County in Kenya. Data were audio-recorded, transcribed and analysed using a framework thematic approach. We found that the priorities of the policy were mainly to meet a political campaign agenda but also align them with the objectives of the country’s legal and policy-guiding instruments and the global goals of SDGs that sought to improve the quality of maternal and neonatal care and eliminate financial barriers. The policy also sought to enhance access to skilled birth attendance (SBA), and its redesign filled the challenge of the previous policy. The stakeholders (bureaucrats, professional bodies, public and developmental partners) influenced the processes of the formulation and the content of the policy through their power to put forward and advocate for specific ideas through issues framed in a political and socioeconomic context. Several stakeholders played different roles in the formulation and implementation based on their interests, power and position in the ecosystem of the policy. Policy formulation or change requires the agents to work within the relevant context, stakeholder interests, power, ideas and framing of issues.
Health outcomes in Deaf signing populations: a systematic review
Authors: Rogers Katherine D , Rowlandson Aleix , Harkness James , Shields Gemma , Young Alys 
Published: January 2024

ABSTRACTObjectives(i) To identify peer reviewed publications reporting the mental and/or physical health outcomes of Deaf adults who are sign language users and to synthesise evidence; (ii) If data available, to analyse how the health of the adult Deaf population compares to that of the general population; (iii) to evaluate the quality of evidence in the identified publications; (iv) to identify limitations of the current evidence base and suggest directions for future research.DesignSystematic review.Data sourcesMedline, Embase, PsychINFO, and Web of ScienceEligibility criteria for selecting studiesThe inclusion criteria were Deaf adult populations who used a signed language, all study types, including methods-focused papers which also contain results in relation to health outcomes of Deaf signing populations. Full-text articles, published in peer-review journals were searched up to 13thJune 2023, published in English or a signed language such as ASL (American Sign Language).Data extractionSupported by the Rayyan systematic review software, two authors independently reviewed identified publications at each screening stage (primary and secondary). A third reviewer was consulted to settle any disagreements. Comprehensive data extraction included research design, study sample, methodology, findings, and a quality assessment.ResultsOf the 35 included studies, the majority (25 out of 35) concerned mental health outcomes. The findings from this review highlighted the inequalities in health and mental health outcomes for Deaf signing populations in comparison with the general population, gaps in the range of conditions studied in relation to Deaf people, and the poor quality of available data.ConclusionsPopulation sample definition and consistency of standards of reporting of health outcomes for Deaf people who use sign language should be improved. Further research on health outcomes not previously reported is needed to gain better understanding of Deaf people’s state of health.Strengths and limitations of this studyThis is the first systematic review of health and mental health outcomes that focused solely on evidence concerning Deaf adults who are sign language users as a distinct population rather than their incorporation within broader based health outcomes studies about deaf people in general. The review is international in scope and covers the health outcomes of Deaf adult sign language users across the globe.This systematic review was carried out following the PRISMA guidelines by a multidisciplinary team of Deaf and hearing health service researchers from varied backgrounds.The weakness of many studies is clearly distinguishing the population of deaf sign language users within their samples, results in discarding some evidence that might have otherwise been helpful.Original protocol for the studyProspero registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=182609
The effect of proactive, interactive, two-way texting on 12-month retention in antiretroviral therapy: findings from a quasi-experimental study in Lilongwe, Malawi
Authors: Feldacker Caryl , Klabbers Robin E. , Huwa Jacqueline , Kiruthu-Kamamia Christine , Thawani Agness , Tembo Petros , Chintedza Joseph , Chiwaya Geldert , Kudzala Aubrey , Bisani Pachawo , Ndhlovu Dumisani , Seyani Johnnie , Tweya Hannock 
Published: January 2024

AbstractBackgroundRetaining clients on antiretroviral therapy (ART) is challenging especially during the first year on ART. Mobile health (mHealth) interventions show promise to close retention gaps. We aimed to assess reach (who received the intervention?) and effectiveness (did it work?) of a hybrid two-way texting (2wT) intervention to improve ART retention at a large public clinic in Lilongwe, Malawi.MethodsBetween August 2021 - June 2023, a quasi-experimental study compared outcomes between two cohorts of new ART clients: 1) those opting into 2wT with combined automated, weekly motivation short messaging service (SMS) messages and response-requested appointment reminders; and 2) a matched historical cohort receiving standard of care (SoC).Reachwas defined as “the proportion clients ≤6 months of ART initiation eligible for 2wT”. 2wTeffectivenesswas assessed in time-to-event analysis comparing Kaplan-Meier plots of 6- and 12-month retention between 2wT and SoC using a log-rank test. The effect of 2wT on ART drop out was estimated using multivariable Cox proportional hazard models, adjusting for sex, age and WHO stage at ART initiation.ResultsOf the 1,146 clients screened, 645 were ineligible (56%) largely due to lack of phone access (393/645; 61%) and illiteracy (149/645; 23%): a reach of 44%. Among 468 2wT participants, the 12-month probability of ART retention was 91% (95%CI: 88% - 93%) compared to 75% (95%CI: 71% - 79%) among 468 SoC participants (p<0.0001). Compared to SoC participants, 2wT participants had a 62% lower hazard of dropping out of ART care at all time points (hazard ratio 0.38, 95% CI: 0.26-0.54; p<0.001).ConclusionsNot all clients were reached with 2wT. For those who opted-in, 2wT reduced drop out throughout the first year on ART and significantly increased 12-month retention. The proactive 2wT approach should be expanded as a complement to other interventions in routine, low-resource settings to improve ART retention.
Genetic mapping of the powdery mildew resistance gene Pm13 on oat chromosome 1D
Authors: Schurack Selma , Beuch Steffen , Cowan Sandy , Griffiths Irene , Lunzer Magdalena , Morales Laura , Tudor Sara , Buerstmayr Hermann , Howarth Catherine J , Tinker Nicholas A , Herrmann Matthias H 
Published: January 2024

AbstractPowdery mildew, caused by the biotrophic fungusBlumeria graminisDC. f. sp.avenae, is a widespread disease of oats, especially in the temperate regions of Western and Central Europe, and the use of resistant varieties is the most sustainable way to ensure stable yields. Therefore, the identification of robust and effective resistance to powdery mildew is of great interest for oat breeding. In contrast to race-specific resistance genes, adult plant resistance (APR) is generally considered to be more durable. The oat variety Firth, as well as related varieties such as Husky or Flämingstip, contains an unknown APR gene, which was previously located on chromosome 1D using DArT markers. The aim of this study was to confirm and refine the chromosomal location of this resistance gene, tentatively named Pm13. To this end, two independent experiments were carried out using different genetic material under natural infection conditions in the field: genome-wide association mapping (GWAS) in a diverse set of 250 oat lines grown in ten environments and QTL mapping in a HuskyxAVE1284 bi-parental population grown in three environments. Both approaches identified a QTL for powdery mildew resistance on the distal end of chromosome 1D in the hexaploid Sang oat genome. The locus explained up to 15 % of the phenotypic variance in GWAS and 64 % of the phenotypic variance in QTL mapping. Comparison of field data with results from laboratory leaf segment tests confirmed that Pm13 does indeed confer APR. The sequence information of the identified linked markers may allow the development of molecular markers useful for early selection of oat lines with high levels of APR.
KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system
Authors: Chakraborty Avirup , Yang Changlin , Kresak Jesse L. , Silver Aryeh , Feier Diana , Tian Guimei , Andrews Michael , Sobanjo Olusegun O. , Hodge Ethan D. , Engelbart Mia K. , Huang Jianping , Harrison Jeffrey K. , Sarkisian Matthew R. , Mitchell Duane A. , Deleyrolle Loic P. 
Published: January 2024

ABSTRACTGlioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment-resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor-microenvironment (TME) underline their significance, driven by their unique properties.This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy.Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM-pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.
A novel approach for simultaneous detection of structural and single-nucleotide variants based on a combination of chromosome conformation capture and exome sequencing
Authors: Gridina Maria , Lagunov Timofey , Belokopytova Polina , Torgunakov Nikita , Nuriddinov Miroslav , Nurislamov Artem , Nazarenko Lyudmila P , Kashevarova Anna A , Lopatkina Maria E , Belyaeva Elena O , Salyukova Olga A , Cheremnykh Aleksandr D , Suhanova Natalia N. , Minzhenkova Marina E , Markova Zhanna G , Demina Nina A. , Stepanchuk Yana , Khabarova Anna , Yan Alexandra , Valeev Emil , Koksharova Galina , Grigor’eva Elena V , Kokh Natalia , Lukjanova Tatiana , Maximova Yulia , Musatova Elizaveta , Shabanova Elena , Kechin Andrey , Khrapov Evgeniy , Boyarskih Uliana , Ryzhkova Oxana , Suntsova Maria , Matrosova Alina , Karoli Mikhail , Manakhov Andrey , Filipenko Maxim , Rogaev Evgeny , Shilova Nadezhda V , Lebedev Igor N , Fishman Veniamin 
Published: January 2024

AbstractEffective molecular diagnosis of congenital diseases hinges on comprehensive genomic analysis, traditionally reliant on various methodologies specific to each variant type—whole exome or genome sequencing for single nucleotide variants (SNVs), array CGH for copy-number variants (CNVs), and microscopy for structural variants (SVs). We introduce a novel, integrative approach combining exome sequencing with chromosome conformation capture, termed Exo-C. This method enables the concurrent identification of SNVs in clinically relevant genes and SVs across the genome and allows analysis of heterozygous and mosaic carriers. Enhanced with targeted long-read sequencing, Exo-C evolves into a cost-efficient solution capable of resolving complex SVs at base-pair accuracy. Through several case studies, we demonstrate how Exo-C’s multifaceted application can effectively uncover diverse causative variants and elucidate disease mechanisms in patients with rare disorders.
Romer-EPTI: rotating-view motion-robust super-resolution EPTI for SNR-efficient distortion-free in-vivo mesoscale dMRI and microstructure imaging
Authors: Dong Zijing , Reese Timothy G. , Lee Hong-Hsi , Huang Susie Y. , Polimeni Jonathan R. , Wald Lawrence L. , Wang Fuyixue 
Published: January 2024

AbstractPurposeTo overcome the major challenges in dMRI acquisition, including low SNR, distortion/blurring, and motion vulnerability.MethodsA novel Romer-EPTI technique is developed to provide distortion-free dMRI with significant SNR gain, high motion-robustness, sharp spatial resolution, and simultaneous multi-TE imaging. It introduces a ROtating-view Motion-robust supEr-Resolution technique (Romer) combined with a distortion/blurring-free EPTI encoding. Romer enhances SNR by a simultaneous multi-thick-slice acquisition with rotating-view encoding, while providing high motion-robustness through a motion-aware super-resolution reconstruction, which also incorporates slice-profile and real-value diffusion, to resolve high-isotropic-resolution volumes. The in-plane encoding is performed using distortion/blurring-free EPTI, which further improves effective spatial resolution and motion robustness by preventing not only T2/T2*-blurring but also additional blurring resulting from combining encoded volumes with inconsistent geometries caused by dynamic distortions. Self-navigation was incorporated to enable efficient phase correction. Additional developments include strategies to address slab-boundary artifacts, achieve minimal TE for SNR gain at 7T, and achieve high robustness to strong phase variations at high b-values.ResultsUsing Romer-EPTI, we demonstrate distortion-free whole-brain mesoscale in-vivo dMRI at both 3T (500-μm-iso) and 7T (485-μm-iso) for the first time, with high SNR efficiency (e.g.,), and high image quality free from distortion and slab-boundary artifacts with minimal blurring. Motion experiments demonstrate Romer-EPTI’s high motion-robustness and ability to recover sharp images in the presence of motion. Romer-EPTI also demonstrates significant SNR gain and robustness in high b-value (b=5000s/mm2) and time-dependent dMRI.ConclusionRomer-EPTI significantly improves SNR, motion-robustness, and image quality, providing a highly efficient acquisition for high-resolution dMRI and microstructure imaging.
QUAL-IF-AI: Quality Control of Immunofluorescence Images using Artificial Intelligence
Authors: Andhari Madhavi Dipak , Rinaldi Giulia , Nazari Pouya , Shankar Gautam , Dubroja Nikolina , Vets Johanna , Ostyn Tessa , Vanmechelen Maxime , Decraene Brecht , Arnould Alexandre , Mestdagh Willem , De Moor Bart , De Smet Frederik , Bosisio Francesca , Antoranz Asier 
Published: January 2024

AbstractFluorescent imaging has revolutionized biomedical research, enabling the study of intricate cellular processes. Multiplex immunofluorescent imaging has extended this capability, permitting the simultaneous detection of multiple markers within a single tissue section. However, these images are susceptible to a myriad of undesired artifacts, which compromise the accuracy of downstream analyses. Manual artifact removal is impractical given the large number of images generated in these experiments, necessitating automated solutions. Here, we present QUAL-IF-AI, a multi-step deep learning-based tool for automated artifact identification and management. We demonstrate the utility of QUAL-IF-AI in detecting four of the most common types of artifacts in fluorescent imaging: air bubbles, tissue folds, external artifacts, and out-of-focus areas. We show how QUAL-IF-AI outperforms state-of-the-art methodologies in a variety of multiplexing platforms achieving over 85% of classification accuracy and more than 0.6 Intersection over Union (IoU) across all artifact types. In summary, this work presents an automated, accessible, and reliable tool for artifact detection and management in fluorescent microscopy, facilitating precise analysis of multiplexed immunofluorescence images.
Impact of IL-21 on Natural Killer cell proliferation and function – a mathematical and functional assessment
Authors: Biondo Rosalba , Nayak Indrani , Möker Nina , Zhang Congcong , Stewart William C. , Khakoo Salim , Das Jayajit 
Published: January 2024

AbstractNatural killer (NK) cells are currently in use as immunotherapeutic agents for cancer. Many different cytokines are used to generate NK cells including IL-2, IL-12, IL-15 and IL-18 in solution and membrane bound IL-21. These cytokines drive NK cell activation through the integration of STAT and NF-κB pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy between STAT3 and NF-κB transcription factors. Use of IL-21 in solution in the priming, but not post-priming phase of NK cell culture resulted in optimal NK cell proliferation, without compromising cytotoxicity or IFN-γ secretion against hepatocellular carcinoma cell lines. Our work provides a mathematical framework for interrogating NK cell activation for cancer immunotherapy.
Impact of juglone on oral carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO) in rat model
Authors: Topal Olgun , Topal Burcu , Baş Yunus , Ongan Bünyamin , Sadi Gökhan , Aslan Esra , Yavaş Betül Demirciler , Pektaş Mehmet Bilgehan 
Published: January 2024

AbstractIn this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model on animals.Wistarrats were divided into five groups; Control, NQO, Juglone, NQO+J, and NQO+J*. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated byrt-qPCRandWestern blot. Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.
reguloGPT: Harnessing GPT for Knowledge Graph Construction of Molecular Regulatory Pathways
Authors: Wu Xidong , Zeng Yiming , Das Arun , Jo Sumin , Zhang Tinghe , Patel Parth , Zhang Jianqiu , Gao Shou-Jiang , Pratt Dexter , Chiu Yu-Chiao , Huang Yufei 
Published: January 2024

AbstractMotivationMolecular Regulatory Pathways (MRPs) are crucial for understanding biological functions. Knowledge Graphs (KGs) have become vital in organizing and analyzing MRPs, providing structured representations of complex biological interactions. Current tools for mining KGs from biomedical literature are inadequate in capturing complex, hierarchical relationships and contextual information about MRPs. Large Language Models (LLMs) like GPT-4 offer a promising solution, with advanced capabilities to decipher the intricate nuances of language. However, their potential for end-to-end KG construction, particularly for MRPs, remains largely unexplored.ResultsWe present reguloGPT, a novel GPT-4 based in-context learning prompt, designed for the end-to-end joint name entity recognition, N-ary relationship extraction, and context predictions from a sentence that describes regulatory interactions with MRPs. Our reguloGPT approach introduces a context-aware relational graph that effectively embodies the hierarchical structure of MRPs and resolves semantic inconsistencies by embedding context directly within relational edges. We created a benchmark dataset including 400 annotated PubMed titles on N6-methyladenosine (m6A) regulations. Rigorous evaluation of reguloGPT on the benchmark dataset demonstrated marked improvement over existing algorithms. We further developed a novel G-Eval scheme, leveraging GPT-4 for annotation-free performance evaluation and demonstrated its agreement with traditional annotation-based evaluations. Utilizing reguloGPT predictions on m6A-related titles, we constructed the m6A-KG and demonstrated its utility in elucidating m6A’s regulatory mechanisms in cancer phenotypes across various cancers. These results underscore reguloGPT’s transformative potential for extracting biological knowledge from the literature.Availability and implementationThe source code of reguloGPT, the m6A title and benchmark datasets, and m6A-KG are available at:https://github.com/Huang-AI4Medicine-Lab/reguloGPT.