bluuebunny/crossref_metadata_2025 huggingface dataset:
Far-infrared stimulation of Neiguan acupoints improves heart rate variability and ameliorate fatigue in hemodialysis patients: A randomized trial
Authors: Liao Ling-Yu , Chien Li-Wei , Liu Chi-Feng
Published: January 2024

Background:

In 2018, 84 615 patients in Taiwan received hemodialysis, of which about 62% to 97% suffered from fatigue. Fatigue caused by hemodialysis may be mental or physical. However, the detailed mechanism remains unclear. This study aimed to evaluate whether far-infrared stimulation of the Neiguan acupoint (P6) could effectively reduce fatigue and improve heart rate variability (HRV) in hemodialysis patients.

Methods:

We conducted a two-arm, randomized trial in a hemodialysis center between March 2015 and March 2016. A total of 73 hemodialysis patients were included and were randomly assigned to an experimental group (n = 37) and a control group (n = 36). The experimental group received far-infrared radiation on Neiguan acupoint during hemodialysis for 12 weeks. The outcomes were fatigue level and HRV.

Results:

All patients showed moderate fatigue (M = 26.00 ± 13.01, range = 0-78) at baseline. Far-infrared stimulation on Neiguan acupoint significantly reduced overall fatigue (β = 24, p < 0.001) and improved HRV (β = 74.36, p < 0.001). Compared to the control group, the experiment group had significantly reduced fatigue levels in all aspects such as reduced energy and motivation (β = −2.97, p < 0.001), reduced physical strength (β = −1.28, p < 0.01), reduced mental capability (β = −2.38, p < 0.001), reduction in daily activities (β = −1.48, p < 0.01), depressed mood and loss of control (β = −1.21, p< 0.05) as well as increased autonomous nervous system activity (β = 14.71, p < 0.01) in the third month of stimulation.

Conclusion:

Far-infrared stimulation of the Neiguan acupoints effectively reduces fatigue and increases autonomic nervous system activity in hemodialysis patients.
Cannabis use in liver transplant candidates and recipients
Authors: Kriss Michael , Shingina Alexandra , Hamel Stephanie , Winder Gerald Scott
Published: January 2024

The increasing legality and acceptance of cannabis sale and consumption across the United States has led to a measurable increase in cannabis use nationwide, including in liver transplant (LT) candidates and recipients. With over 75% of liver transplant recipients transplanted in states with legalized use of medicinal and/or recreational cannabis, liver transplant clinicians must have expertise in the assessment of cannabis use given its potential impact on clinical care. In this review, the authors provide an understanding of nomenclature and tools to assess cannabis use, highlight essential components to guide clinical policy development and implementation, and discuss the potential impacts of cannabis use on patients’ transplant course.
Lack of Identity and Suicidality
Authors: Russolillo Angela , Spidel Alicia , Kealy David
Published: January 2024

Identity disturbance has been connected to both psychological distress and suicidality, and associated with emotion dysregulation. However, despite empirical evidence of a relationship between lack of identity and poor psychiatric outcomes, the link between impaired identity and emotion dysregulation in suicide risk remains underexplored, particularly among individuals seeking outpatient mental health services. Using data from a large clinical sample (n = 246), the present study examined the association between lack of identity and suicidality and the role of emotion dysregulation within this process. Findings indicated that the mediation model was significant, with emotion regulation difficulties significantly mediating the association between lack of identity and future suicidal behavior. Furthermore, the indirect effect of lack of identity on anticipated suicidality remained significant beyond general distress and past suicide attempt. Our findings add to the literature examining the complex relationship among lack of identity, emotion regulation, and suicidality.
The Effect of Teach-Back on Readmission Rates in Rehabilitation Patients
Authors: Bidlespacher Kelly , Mulkey David C.
Published: January 2024

Purpose

Thirty-day readmissions often occur in rehabilitation patients and can happen for many reasons. One of those reasons is when patients do not fully understand how to effectively manage their health after discharge. The purpose of this evidence-based quality improvement project was to determine if implementing the teach-back intervention from the Agency for Healthcare Research and Quality’s (AHRQ) Health Literacy Universal Precautions Toolkit would impact 30-day readmission rates among adult rehabilitation patients.

Methods

Data were collected from the electronic health record of rehabilitation patients. The comparative group included all rehabilitation admissions for 8 weeks prior to the intervention. The implementation group was composed of the rehabilitation admissions for 8 weeks post-implementation. All patients were then followed for 30 days postdischarge to capture readmissions.

Results

The total sample size was 79 (n = 43 in the comparative group, n = 36 in the implementation group). There was a 45% decrease in the mean percentage of the 30-day readmission rate in the implementation group as compared with the comparative group

Conclusion

Based on the results, using the teach-back intervention from AHRQ’s Health Literacy Universal Precautions Toolkit may impact 30-day readmission rates.
Causal association of attention-deficit/hyperactivity disorder and autism spectrum disorder with post-traumatic stress disorder
Authors: Song Yuqing , Zhao Yi , Baranova Ancha , Cao Hongbao , Yue Weihua , Zhang Fuquan
Published: January 2024

Background

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two neurodevelopmental disorders that often result in individuals experiencing traumatic events. However, little is known about the connection between ADHD/ASD and post-traumatic stress disorder (PTSD). This study aimed to investigate the genetic associations between these disorders.

Methods

Genetic correlation analysis was used to examine the genetic components shared between ADHD (38 691 cases and 275 986 controls), ASD (18 381 cases and 27 969 controls) and PTSD (23 212 cases and 151 447 controls). Two-sample Mendelian randomization analyses were employed to explore the bidirectional causal relationships between ADHD/ASD and PTSD.

Results

The results of the genetic correlation analysis revealed significant positive correlations of PTSD with ADHD(rg = 0.70) and ASD (rg = 0.34). Furthermore, the Mendelian randomization analysis revealed that genetic liabilities to ADHD [odds ratio (OR) = 1.14; 95% confidence interval (CI), 1.06–1.24; P = 7.88 × 10−4] and ASD (OR = 1.04; CI, 1.01–1.08; P = 0.014) were associated with an increased risk of developing PTSD later in life. However, no evidence supported that genetic liability to PTSD could elevate the risk of ADHD or ASD.

Conclusion

The findings of this study supported that ADHD and ASD may increase the risk of PTSD, but not vice versa.
Identification of Salmonella enterica biovars Gallinarum and Pullorum and their antibiotic resistance pattern in integrated crop-livestock farms and poultry meats
Authors: Julianingsih Dita , Alvarado-Martinez Zabdiel , Tabashsum Zajeba , Tung Chuan-Wei , Aditya Arpita , Kapadia Sarika , Maskey Saloni , Mohapatra Aditi , Biswas Debabrata
Published: January 2024

Due to consumer demand, many conventional poultry farms are now growing poultry without antibiotics or synthetic chemicals. In addition to this, pasture/organic poultry farms have increased significantly in the USA, and they are also antibiotic- and chemical-free. According to recent reports, both antibiotic-free conventional and pasture poultry farmers are facing the reemergence of bacterial diseases. Bacterial diseases cause higher mortality rates in birds and lead to non-profitable poultry farming. This study investigated the prevalence of Salmonella enterica subsp. enterica serovar Gallinarum biovars Gallinarum (S. Gallinarum), the causative agent of fowl typhoid, and Salmonella enterica subsp. enterica serovar Gallinarum biovars Pullorum (S. Pullorum), the causative agent of pullorum disease, within integrated crop-livestock/pasture farm environments and their processed products. A total of 1,286 samples were collected from 6 farms and adjacent 13 markets to determine the prevalence of S. Gallinarum and S. Pullorum by using both microbiological culture and molecular techniques. Antibiotic resistance pattern of the confirmed isolates was subsequently determined with an antibiogram assay following the Clinical Laboratory Standards Institute guidelines for relevant antibiotics. S. Pullorum was detected in 11 samples (2.7%), while S. Gallinarum was found in 6 samples (1.5%) out of a total of 403 samples at the pre-harvest level. At the post-harvest level, only S. Gallinarum was identified in 14 meat samples out of 883 (1.6%) recovered from samples collected from retail markets. Antibiogram showed S. Gallinarum and S. Pullorum to be highly resistant to cephradine, trimethoprim-sulfamethoxazole, amoxicillin, streptomycin, and ampicillin. This data demonstrates that both S. Pullorum and S. Gallinarum are commonly present in farm poultry environments as well as the products sold in the markets, which warrants implementation of regular surveillance and monitoring programs, as well as potentially requiring future control strategies to reduce S. Pullorum and S. Gallinarum transmission.
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

Kenya 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

Objectives

(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.

Design

Systematic review.

Data sources

Medline, Embase, PsychINFO, and Web of Science

Eligibility criteria for selecting studies

The 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 extraction

Supported 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.

Results

Of 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.

Conclusions

Population 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 study

This 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 study

Prospero 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

Background

Retaining 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.

Methods

Between 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.

Results

Of 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).

Conclusions

Not 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

Powdery 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

Glioblastoma (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

Effective 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

Purpose

To overcome the major challenges in dMRI acquisition, including low SNR, distortion/blurring, and motion vulnerability.

Methods

A 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.

Results

Using 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.

Conclusion

Romer-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

Fluorescent 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

Natural 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

In 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

Motivation

Molecular 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.

Results

We 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 implementation

The source code of reguloGPT, the m6A title and benchmark datasets, and m6A-KG are available at:https://github.com/Huang-AI4Medicine-Lab/reguloGPT.
Integration of hyperspectral imaging and transcriptomics from individual cells with HyperSeq
Authors: Xie Yike , Habibalahi Abbas , Anwer Ayad G. , Wahi Kanu , Gatt Catherine , Johansson Emma M. V. , Holst Jeff , Goldys Ewa , Zanini Fabio
Published: January 2024

Microscopy and omics are complementary approaches to probe the molecular state of cells in health and disease, combining granularity with scalability. While important advances have been achieved over the last decade in each area, integrating both imaging- and sequencing-based assays on the same cell has proven challenging. In this study, a new approach called HyperSeq that combines hyperspectral autofluorescence imaging with transcriptomics on the same cell is demonstrated. HyperSeq was applied to Michigan Cancer Foundation 7 (MCF-7) breast cancer cells and identified a subpopulation of cells exhibiting bright autofluorescence rings at the plasma membrane in optical channel 13 (λex= 431 nm,λem= 594 nm). Correlating the presence of a ring with the gene expression in the same cell indicated that ringed cells are more likely to express hallmark genes of apoptosis and less likely to express genes associated with ATP production. Further, correlation of cell morphology with gene expression suggested that multiple members of the spliceosome were downregulated in larger MCF-7 cells. Multiple genes were evenly expressed across cell sizes but also exhibited higher usage of specific exons in larger or smaller cells. Finally, correlation between gene expression and fluorescence within the spectral range of Nicotinamide adenine dinucleotide hydrogen (NADH) provided insight into the metabolic states of MCF-7 cells. These observations provided a link between the cell’s optical spectrum and its internal molecular state, demonstrating the utility of HyperSeq to study cell biology at single cell resolution by integrating spectral, morphological and transcriptomic analyses into a single, streamlined workflow.
A unified model for cell-type resolution genomics from heterogeneous omics data
Authors: Chen Zeyuan Johnson , Rahmani Elior , Halperin Eran
Published: January 2024

The vast majority of population-scale genomic datasets collected to date consist of “bulk” samples obtained from heterogeneous tissues, reflecting mixtures of different cell types. In order to facilitate discovery at the cell-type level, there is a pressing need for computational deconvolution methods capable of leveraging the multitude of underutilized bulk profiles already collected across various organisms, tissues, and conditions. Here, we introduce Unico, a unified cross-omics method designed to deconvolve standard 2-dimensional bulk matrices of samples by features into 3-dimensional tensors representing samples by features by cell types. Unico stands out as the first principled model-based deconvolution method that is theoretically justified for any heterogeneous genomic data. Through the deconvolution of bulk gene expression and DNA methylation datasets, we demonstrate that the transferability of Unico across different data modalities translates into superior performance compared to existing approaches. This advancement enhances our capability to conduct powerful large-scale genomic studies at cell-type resolution without the need for cell sorting or single-cell biology. An R implementation of Unico is available on CRAN.
Policy approaches to decarbonising the transport sector in Aotearoa/NZ: Equity, health and health system impacts
Authors: Shaw Caroline , Mizdrak Anja , Gage Ryan , McLeod Melissa , Jones Rhys , Woodward Alistair , Cobiac Linda
Published: January 2024

Background

Health co-benefits are a key potential advantage of transport decarbonisation policy. However, health impacts will occur in the context of existing transport-health inequities and decarbonisation policies will themselves impact inequities.

Methods

We modelled the health, health system and environmental impacts of the ‘Behaviour’ and ‘Technology’ pathways developed by the New Zealand Climate Change Commission. Household transport related health impacts were modelled through the pathways of physical activity, air pollution (PM2·5and NO2) and injury for the New Zealand population from 2018 to 2050. We modelled impacts for Māori (the Indigenous Peoples of Aotearoa) and non-Māori.

Findings

Both pathways show improvements in population health, reductions in health system costs and reduced lifecycle greenhouse gas emissions compared to baseline, although health gains were substantially larger in the Behaviour pathway. Health gains were 20-30% larger for Māori than non-Māori in both pathways, although more healthy life years were gained by Māori in the Behaviour pathway. For those aged 0-4 in 2018, healthy life expectancy differences between Māori and non-Māori reduced by 0·5% in the Behaviour pathway. Healthy life years gained by Māori and non-Māori altered substantially depending on assumptions about the equity of the implemented pathway.

Interpretation

Decarbonising transport may reduce health and healthy life expectancy inequities between Māori and non-Māori if policies supporting decarbonisation are implemented equitably. Pathways that increase physical activity will have a much larger impact on population health than those which rely on low emission vehicles.Funding:Health Research Council of New Zealand (20/151) and University of Otago.
Yellow fever in Ghana: Predicting emergence and ecology from historical outbreaks
Authors: Judson Seth D. , Kenu Ernest , Fuller Trevon , Asiedu-Bekoe Franklin , Biritwum-Nyarko Alberta , Schroeder Lee F. , Dowdy David W.
Published: January 2024

Understanding the epidemiology and ecology of yellow fever in endemic regions is critical for preventing future outbreaks. Ghana is a high-risk country for yellow fever. In this study we estimate the epidemiology, ecological cycles, and areas at risk for yellow fever in Ghana based on historical outbreaks. We identify 2371 cases and 887 deaths (case fatality rate 37.4%) from yellow fever reported in Ghana from 1910 to 2022. Since implementation of routine childhood vaccination in 1992, the estimated mean annual number of cases decreased by 81% and the geographic distribution of yellow fever cases also changed. While there have been multiple large historical outbreaks of yellow fever in Ghana from the urban cycle, recent outbreaks have originated among unvaccinated nomadic groups in rural areas with the sylvatic/savanna cycles. Using machine learning and an ecological niche modeling framework, we predict areas in Ghana that are similar to where prior yellow fever outbreaks have originated based on temperature, precipitation, landcover, elevation, and human population density. We find differences in predictions depending on the ecological cycles of outbreaks. Ultimately, these findings and methods could be used to inform further subnational risk assessments for yellow fever in Ghana and other high-risk countries.

Author Summary

Yellow fever is a viral hemorrhagic fever transmitted by mosquitoes in Africa and South America through different ecological transmission cycles. While West Africa has had the most cases of yellow fever, less is known about the epidemiology and ecology of yellow fever among countries in this region. Ghana has had multiple yellow fever outbreaks, including a recent outbreak in 2021-2022. In this study we estimate cases and deaths due to yellow fever in Ghana, compare the ecological cycles of outbreaks, and predict future areas at risk based on prior yellow fever cases and environmental conditions. We find that the populations at risk for yellow fever in Ghana have changed over the past century and that different ecological factors influence the risk of future emergence. Understanding these changes and the nuances of yellow fever epidemiology and ecology within countries will be important for future outbreak preparedness.
Discovering additional genetic loci associated with six psychiatric disorders/traitsviaFDR regression model leveraging external genetic and biological data
Authors: Rao Shi-tao , Qiu Jing-hong , Zhi Yi-qiang , Lin Yu-ping , Zhang Ruo-yu , Chen Xiao-tong , Xu Dan , So Hon-Cheong
Published: January 2024

Background

Common psychiatric disorders have substantial heritability influenced by multiple genes. While a number of susceptibility variants have been identified, many associated variants remain undiscovered. This study aimed to identify additional genetic loci associated with common psychiatric disorders/traits by leveraging correlated traits and biological annotations.

Methods

We proposed application of the false discovery rate (FDR) regression model to uncover additional genetic loci for six psychiatric disorders/traits. To enhance the likelihood of discovering additional significant genetic loci and genes, we utilized a set of 42 correlated traits and 21 biological annotations as covariates. Internal validation analysis and drug cluster enrichment analysis were conducted to validate the biological significance of the additional genetic loci/genes uncovered. We also experimentally validated two additional genes revealed for autism spectrum disorder (ASD).

Results

The FDR regression (FDRreg) analysis strategy revealed hundreds of additional significant genes (FDR<0.01) in gene-level analyses, surpassing the number of significant genes found in the original studies. Specifically, in 11/16 trait analyses, FDRreg identified more significant genes based on gene-based analysis with MAGMA, and in 12/16 analyses, FDRreg identified more significant genes based on imputed expression in the brain. In SNP-level results, the majority of analyses (13/16) identified an equal or higher number of genomic risk loci (FDR<0.01). We found that FDRreg is able to reveal genes that are later known to be significant in subsequent larger-scale GWAS. Drug cluster enrichment analysis demonstrated a stronger enrichment in psychiatry-related drug clusters. In utero electroporation (IUE) experiments provided evidence to support two additional genes identified for ASD in critical embryonic brain development processes.

Conclusions

By integrating genetically correlated traits and biological annotations, the FDRreg strategy enables the identification of a greater number of additional significant genes and risk loci. Moreover, the new associated genes exhibited meaningful biological and clinical implications. This study presents a valuable approach for uncovering the genetic basis of psychiatric disorders and gaining insights into their underlying biology.
Reliability of single-lead electrocardiogram interpretation to detect atrial fibrillation: insights from the SAFER Feasibility Study
Authors: Hibbitt Katie , Brimicombe James , Cowie Martin R. , Dymond Andrew , Freedman Ben , Griffin Simon J , Hobbs FD Richard , Lindén Hannah Clair , Lip Gregory Y. H. , Mant Jonathan , McManus Richard J. , Pandiaraja Madhumitha , Williams Kate , Charlton Peter H.
Published: January 2024

Background and Aims

Single-lead electrocardiograms (ECGs) can be recorded using widely available devices such as smartwatches and handheld ECG recorders. Such devices have been approved for atrial fibrillation (AF) detection. However, little evidence exists on the reliability of single-lead ECG interpretation. We aimed to assess the level of agreement on detection of AF by independent cardiologists interpreting single lead ECGs, and to identify factors influencing agreement.

Methods

In a population-based AF screening study, adults aged ≥65 years old recorded four single-lead ECGs per day for 1-4 weeks using a handheld ECG recorder. ECGs showing signs of possible AF were identified by a nurse, aided by an automated algorithm. These were reviewed by two independent cardiologists who assigned participant- and ECG-level diagnoses. Inter-rater reliability of AF diagnosis was calculated using linear weighted Cohen’s kappa (κw).

Results

Out of 2,141 participants and 162,515 ECGs, only 1,843 ECGs from 185 participants were reviewed by both cardiologists. Agreement was moderate:κw= 0.42 (95% CI, 0.32 – 0.52) at participant-level; andκw= 0.51 (0.46 – 0.56) at ECG-level. At participant-level, agreement was associated with the number of adequate-quality ECGs recorded, with higher agreement in participants who recorded at least 67 adequate-quality ECGs. At ECG-level, agreement was associated with ECG quality and whether ECGs exhibited algorithm-identified possible AF.

Conclusion

Inter-rater reliability of AF diagnosis from single-lead ECGs was found to be moderate in older adults. Strategies to improve reliability might include participant and cardiologist training and designing AF detection programmes to obtain sufficient ECGs for reliable diagnoses.

What’s New

We observed moderate agreement between cardiologists when diagnosing AF from single-lead ECGs in an AF screening study.

This study indicates that for every 100 screening participants diagnosed with AF by two cardiologists, there would be complete disagreement over the diagnosis of 70 further participants.

We found that the quality of ECG signals greatly influenced the reliability of single-lead ECG interpretation.

In addition, when multiple ECGs were acquired from an individual, the reliability of participant-level diagnoses was influenced by the number of adequate-quality ECGs available for interpretation.
Quality measures of two-stage newborn hearing screening: Systematic review with a Bayesian meta-analysis
Authors: Manz Kirsi , Nennstiel Uta , Marzi Carola , Mansmann Ulrich , Brockow Inken
Published: January 2024

Background

Newborn Screening for hearing impairment (NHS) is a crucial public health issue worldwide. Often, a two-stage screening with two different testing approaches is used. We aimed to investigate the optimal screening algorithm, based on data from the literature published in the last 30 years. A particular focus of the study was to synthesize the existing evidence on two-stage newborn hearing screening regarding the refer rate (RFR), the percentage of children that did not pass the second test or were lost after the first test.

Methods

We searched MEDLINE and Scopus for studies on two-stage NHS using transitory evoked otoacoustic emissions (TEOAE) or automated auditory brainstem response (AABR). All studies on newborns who received their first test as an inpatient and a second test up to one month later were eligible. Random effects meta-analysis and Bayesian modeling were performed to estimate RFR as well as effects of the second test phase on the RFR. Risk of bias was assessed using QUADAS-II. The unfunded study was registered in PROSPERO (CRD42023403091).

Results

Eighty-five study protocols, including over 1,12 million newborns, met the inclusion criteria. Certainty in the evidence was rated as moderate. The RFR was higher when the test method was changed than without a change of method (AABR-AABR: RFR = 1.3% (95% confidence interval (CI): 0.9, 1.8%), TEOAE-TEOAE: RFR = 2.7% (CI: 2.2, 3.2%), TEOAE-AABR: RFR = 3.9% (CI: 2.9, 5.1%), AABR-TEOAE: 5.9% (CI: 5.0, 6.9%).

Conclusions

Strategies that did not involve changes to the screening method had lower RFR.